Synthesis of new 1,2,4-triazole compounds containing Schiff and Mannich bases (morpholine) with antioxidant and antimicrobial activities.

PubMed

Ünver, Yasemin; Deniz, Sadik; Çelik, Fatih; Akar, Zeynep; Küçük, Murat; Sancak, Kemal

2016-01-01

Compound 2 was synthesized by reacting CS 2 /KOH with compound 1. The treatment of compound 2 with hydrazine hydrate produced compound 3. Then, compound 3 was converted to Schiff bases (4a-d) by the handling with several aromatic aldehydes. The treatment of triazole compounds 4a-d containing Schiff base with morpholine gave compounds 5a-d. All compounds were tested for their antioxidant and antimicrobial activities. The antioxidant test results of DPPH• radical scavenging and ferric reducing/antioxidant power methods showed good antioxidant activity. The triazole-thiol (3) was the most active, and the effect of the substituent type of the thiophene ring on the activity was same for both Schiff bases (4a-d) and Mannich bases (5a-d). Among the newly synthesized triazole derivatives, the Schiff base 4d and the Mannich base 5d carrying nitro substituent on the thiophene ring showed promising antibacterial and antifungal activity, with lower MIC values than the standard antibacterial ampicillin.

Adenovirus-based genetic vaccines for biodefense.

PubMed

Boyer, Julie L; Kobinger, Gary; Wilson, James M; Crystal, Ronald G

2005-02-01

The robust host responses elicited against transgenes encoded by (E1-)(E3-) adenovirus (Ad) gene transfer vectors can be used to develop Ad-based vectors as platform technologies for vaccines against potential bioterror pathogens. This review focuses on pathogens of major concern as bioterror agents and why Ad vectors are ideal as anti-bioterror vaccine platforms, providing examples from our laboratories of using Ad vectors as vaccines against potential bioterror pathogens and how Ad vectors can be developed to enhance vaccine efficacy in the bioterror war.

Disrupted adenovirus-based vaccines against small addictive molecules circumvent anti-adenovirus immunity.

PubMed

De, Bishnu P; Pagovich, Odelya E; Hicks, Martin J; Rosenberg, Jonathan B; Moreno, Amira Y; Janda, Kim D; Koob, George F; Worgall, Stefan; Kaminsky, Stephen M; Sondhi, Dolan; Crystal, Ronald G

2013-01-01

Adenovirus (Ad) vaccine vectors have been used for many applications due to the capacity of the Ad capsid proteins to evoke potent immune responses, but these vectors are often ineffective in the context of pre-existing anti-Ad immunity. Leveraging the knowledge that E1(-)E3(-) Ad gene transfer vectors are potent immunogens, we have developed a vaccine platform against small molecules by covalently coupling analogs of small molecules to the capsid proteins of disrupted Ad (dAd5). We hypothesized that the dAd5 platform would maintain immunopotency even in the context of anti-Ad neutralizing antibodies. To test this hypothesis, we coupled cocaine and nicotine analogs, GNE and AM1, to dAd5 capsid proteins to generate dAd5GNE and dAd5AM1, respectively. Mice were pre-immunized with Ad5Null, resulting in high titer anti-Ad5 neutralizing antibodies comparable to those observed in the human population. The dAd5GNE and dAd5AM1 vaccines elicited high anti-cocaine and anti-nicotine antibody titers, respectively, in both naive and Ad5-immune mice, and both functioned to prevent cocaine or nicotine from reaching the brain of anti-Ad immune mice. Thus, disrupted Ad5 evokes potent humoral immunity that is effective in the context of pre-existing neutralizing anti-Ad immunity, overcoming a major limitation for current Ad-based vaccines.

Access to dialysis services: A systematic mapping review based on geographical information systems.

PubMed

Hoseini, Benyamin; Bagheri, Nasser; Kiani, Behzad; Azizi, Amirabbas; Tabesh, Hamed; Tara, Mahmood

2018-05-07

Equitable access to healthcare services constitutes one of the leading priorities of healthcare provision and access to dialysis services (ADS) has an essential impact on patients depending on renal dialysis. The many existing GIS-based ADS evaluations include various spatial and non-spatial factors affecting ADS. We systematically mapped and reviewed the available literature with reference to this area identifying gaps in current GIS-based ADS measurements and developing recommendations for future studies. A threestep, systematic mapping review of the available GIS-related evidence in PubMed, Embase, Web of science, Scopus, Science Direct and IEEE Xplore was performed in May 2016 and the information collected updated October 2017 by two independent selection processes. The quality of the studies was assessed using an informal, mixed-approach scoring system. Out of 1119 literature references identified, 36 were identified and used for final review after removal of duplicates, study screenings and applying inclusion/exclusion criteria. Given the contents of the selected studies, three study groups were identified and 41 factors with potential effects on ADS determined. These studies mainly addressed the potential and/or spatial aspects of ADS. Our systematic mapping review of the evidence revealed that current GIS-based measures of ADS tend to calculate potential ADS instead of a realized one. It was also noted that listed factors affecting ADS were mainly nonspatial bringing forth the hypothesis that designing an integrated ADS index could possibly produce better ADS score than those currently advocated. Some primary and secondary research suggestions are made and a list of recommendations offered.

Alzheimer's Prevention Education: If We Build It, Will They Come? www.AlzU.org.

PubMed

Isaacson, R S; Haynes, N; Seifan, A; Larsen, D; Christiansen, S; Berger, J C; Safdieh, J E; Lunde, A M; Luo, A; Kramps, M; McInnis, M; Ochner, C N

2014-01-01

Internet-based educational interventions may be useful for impacting knowledge and behavioral change. However, in AD prevention, little data exists about which educational tools work best in terms of learning and interest in participating in clinical trials. Primary: Assess effectiveness of interactive webinars vs. written blog-posts on AD prevention learning. Secondary: Evaluate the effect of AD prevention education on interest in participating in clinical trials; Assess usability of, and user perceptions about, an online AD education research platform; Classify target populations (demographics, learning needs, interests). Observational. Online. Men/Women, aged 25+, recruited via facebook.com. Alzheimer's Universe (www.AlzU.org) education research platform. Pre/post-test performance, self-reported Likert-scale ratings, completion rates. Over two-weeks, 4268 visits were generated. 503 signed-up for a user account (11.8% join rate), 196 participated in the lessons (39.0%) and 100 completed all beta-testing steps (19.9%). Users randomized to webinar instruction about AD prevention and the stages of AD demonstrated significant increases (p=0.01) in pre vs. post-testing scores compared to blog-post intervention. Upon joining, 42% were interested in participating in a clinical trial in AD prevention. After completing all beta-test activities, interest increased to 86%. Users were primarily women and the largest category was children of AD patients. 66.3% joined to learn more about AD prevention, 65.3% to learn more about AD treatment. Webinar-based education led to significant improvements in learning about AD prevention and the stages of AD. AlzU.org participation more than doubled interest in AD prevention clinical trial participation. Subjects were quickly and cost-effectively recruited, and highly satisfied with the AD education research platform. Based on these data, we will further refine AlzU.org prior to public launch and aim to study the effectiveness of 25 interactive webinar-based vs. blog-post style lessons on learning and patient outcomes, in a randomized, within-subjects design trial.

RGD capsid modification enhances mucosal protective immunity of a non-human primate adenovirus vector expressing Pseudomonas aeruginosa OprF

PubMed Central

Krause, A; Whu, W Z; Qiu, J; Wafadari, D; Hackett, N R; Sharma, A; Crystal, R G; Worgall, S

2013-01-01

Replication-deficient adenoviral (Ad) vectors of non-human serotypes can serve as Ad vaccine platforms to circumvent pre-existing anti-human Ad immunity. We found previously that, in addition to that feature, a non-human primate-based AdC7 vector expressing outer membrane protein F of P. aeruginosa (AdC7OprF) was more potent in inducing lung mucosal and protective immunity compared to a human Ad5-based vector. In this study we analysed if genetic modification of the AdC7 fibre to display an integrin-binding arginine–glycine–aspartic acid (RGD) sequence can further enhance lung mucosal immunogenicity of AdC7OprF. Intratracheal immunization of mice with either AdC7OprF.RGD or AdC7OprF induced robust serum levels of anti-OprF immunoglobulin (Ig)G up to 12 weeks that were higher compared to immunization with the human vectors Ad5OprF or Ad5OprF.RGD. OprF-specific cellular responses in lung T cells isolated from mice immunized with AdC7OprF.RGD and AdC7OprF were similar for T helper type 1 (Th1) [interferon (IFN)-γ in CD8+ and interleukin (IL)-12 in CD4+], Th2 (IL-4, IL-5 and IL-13 in CD4+) and Th17 (IL-17 in CD4+). Interestingly, AdC7OprF.RGD induced more robust protective immunity against pulmonary infection with P. aeruginosa compared to AdC7OprF or the control Ad5 vectors. The enhanced protective immunity induced by AdC7OprF.RGD was maintained in the absence of alveolar macrophages (AM) or CD1d natural killer T cells. Together, the data suggest that addition of RGD to the fibre of an AdC7-based vaccine is useful to enhance its mucosal protective immunogenicity. PMID:23607394

Assessing the relationship between ad volume and awareness of a tobacco education media campaign

PubMed Central

Modayil, Mary V; Stevens, Colleen

2010-01-01

Background The relation between aided ad recall and level of television ad placement in a public health setting is not well established. We examine this association by looking back at 8 years of the California's Tobacco Control Program's (CTCP) media campaign. Methods Starting in July 2001, California's campaign was continuously monitored using five telephone series of surveys and six web-based series of surveys immediately following a media flight. We used population-based statewide surveys to measure aided recall for advertisements that were placed in each of these media flights. Targeted rating points (TRPs) were used to measure ad placement intensity throughout the state. Results Cumulative TRPs exhibited a stronger relation with aided ad recall than flight TRPs or TRP density. This association increased after log-transforming cumulative TRP values. We found that a one-unit increase in log-cumulative TRPs led to a 13.6% increase in aided ad recall using web-based survey data, compared to a 5.3% increase in aided ad recall using telephone survey data. Conclusions In California, the relation between aided ad recall and cumulative TRPs showed a diminishing return after a large volume of ad placements These findings may be useful in planning future ad placement for CTCP's media campaign. PMID:20382649

Measuring Value Added in Higher Education: A Proposed Methodology for Developing a Performance Indicator Based on the Economic Value Added to Graduates

ERIC Educational Resources Information Center

Rodgers, Timothy

2007-01-01

The 2003 UK higher education White Paper suggested that the sector needed to re-examine the potential of the value added concept. This paper describes a possible methodology for developing a performance indicator based on the economic value added to graduates. The paper examines how an entry-quality-adjusted measure of a graduate's…

Disrupted Adenovirus-Based Vaccines Against Small Addictive Molecules Circumvent Anti-Adenovirus Immunity

PubMed Central

De, Bishnu P.; Pagovich, Odelya E.; Hicks, Martin J.; Rosenberg, Jonathan B.; Moreno, Amira Y.; Janda, Kim D.; Koob, George F.; Worgall, Stefan; Kaminsky, Stephen M.; Sondhi, Dolan

2013-01-01

Abstract Adenovirus (Ad) vaccine vectors have been used for many applications due to the capacity of the Ad capsid proteins to evoke potent immune responses, but these vectors are often ineffective in the context of pre-existing anti-Ad immunity. Leveraging the knowledge that E1−E3− Ad gene transfer vectors are potent immunogens, we have developed a vaccine platform against small molecules by covalently coupling analogs of small molecules to the capsid proteins of disrupted Ad (dAd5). We hypothesized that the dAd5 platform would maintain immunopotency even in the context of anti-Ad neutralizing antibodies. To test this hypothesis, we coupled cocaine and nicotine analogs, GNE and AM1, to dAd5 capsid proteins to generate dAd5GNE and dAd5AM1, respectively. Mice were pre-immunized with Ad5Null, resulting in high titer anti-Ad5 neutralizing antibodies comparable to those observed in the human population. The dAd5GNE and dAd5AM1 vaccines elicited high anti-cocaine and anti-nicotine antibody titers, respectively, in both naive and Ad5-immune mice, and both functioned to prevent cocaine or nicotine from reaching the brain of anti-Ad immune mice. Thus, disrupted Ad5 evokes potent humoral immunity that is effective in the context of pre-existing neutralizing anti-Ad immunity, overcoming a major limitation for current Ad-based vaccines. PMID:23140508

Metrix Matrix: A Cloud-Based System for Tracking Non-Relative Value Unit Value-Added Work Metrics.

PubMed

Kovacs, Mark D; Sheafor, Douglas H; Thacker, Paul G; Hardie, Andrew D; Costello, Philip

2018-03-01

In the era of value-based medicine, it will become increasingly important for radiologists to provide metrics that demonstrate their value beyond clinical productivity. In this article the authors describe their institution's development of an easy-to-use system for tracking value-added but non-relative value unit (RVU)-based activities. Metrix Matrix is an efficient cloud-based system for tracking value-added work. A password-protected home page contains links to web-based forms created using Google Forms, with collected data populating Google Sheets spreadsheets. Value-added work metrics selected for tracking included interdisciplinary conferences, hospital committee meetings, consulting on nonbilled outside studies, and practice-based quality improvement. Over a period of 4 months, value-added work data were collected for all clinical attending faculty members in a university-based radiology department (n = 39). Time required for data entry was analyzed for 2 faculty members over the same time period. Thirty-nine faculty members (equivalent to 36.4 full-time equivalents) reported a total of 1,223.5 hours of value-added work time (VAWT). A formula was used to calculate "value-added RVUs" (vRVUs) from VAWT. VAWT amounted to 5,793.6 vRVUs or 6.0% of total work performed (vRVUs plus work RVUs [wRVUs]). Were vRVUs considered equivalent to wRVUs for staffing purposes, this would require an additional 2.3 full-time equivalents, on the basis of average wRVU calculations. Mean data entry time was 56.1 seconds per day per faculty member. As health care reimbursement evolves with an emphasis on value-based medicine, it is imperative that radiologists demonstrate the value they add to patient care beyond wRVUs. This free and easy-to-use cloud-based system allows the efficient quantification of value-added work activities. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Alcohol dependence and physical comorbidity: Increased prevalence but reduced relevance of individual comorbidities for hospital-based mortality during a 12.5-year observation period in general hospital admissions in urban North-West England.

PubMed

Schoepf, D; Heun, R

2015-06-01

Alcohol dependence (AD) is associated with an increase in physical comorbidities. The effects of these diseases on general hospital-based mortality are unclear. Consequently, we conducted a mortality study in which we investigated if the burden of physical comorbidities and their relevance on general hospital-based mortality differs between individuals with and without AD during a 12.5-year observation period in general hospital admissions. During 1 January 2000 and 30 June 2012, 23,371 individuals with AD were admitted at least once to seven General Manchester Hospitals. Their physical comorbidities with a prevalence≥1% were compared to those of 233,710 randomly selected hospital controls, group-matched for age and gender (regardless of primary admission diagnosis or specialized treatments). Physical comorbidities that increased the risk of hospital-based mortality (but not outside of the hospital) during the observation period were identified using multiple logistic regression analyses. Hospital-based mortality rates were 20.4% in the AD sample and 8.3% in the control sample. Individuals with AD compared to controls had a higher burden of physical comorbidities, i.e. alcoholic liver and pancreatic diseases, diseases of the conducting airways, neurological and circulatory diseases, diseases of the upper gastrointestinal tract, renal diseases, cellulitis, iron deficiency anemia, fracture neck of femur, and peripheral vascular disease. In contrast, coronary heart related diseases, risk factors of cardiovascular disease, diverticular disease and cataracts were less frequent in individuals with AD than in controls. Thirty-two individual physical comorbidities contributed to the prediction of hospital-based mortality in univariate analyses in the AD sample; alcoholic liver disease (33.7%), hypertension (16.9%), chronic obstructive pulmonary disease (14.1%), and pneumonia (13.3%) were the most frequent diagnoses in deceased individuals with AD. Multiple forward logistic regression analysis, accounting for possible associations of diseases, identified twenty-three physical comorbidities contributing to hospital-based mortality in individuals with AD. However, all these comorbidities had an equal or even lower impact on hospital-based mortality than in the comparison sample. The excess of in-hospital deaths in general hospitals in individuals with AD is due to an increase of multiple physical comorbidities, even though individual diseases have an equal or even reduced impact on general hospital-based mortality in individuals with AD compared to controls. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

[Assessment of a project for integrated management of care given to patients with type-2 diabetes in the Local Health Authority 21 of Legnago (Veneto Region, Northern Italy) in the period 2010-2012].

PubMed

Marcon, Alessandro; Vaona, Alberto; Rigon, Giulio; Carazzolo, Marco; Del Zotti, Franco; Girotto, Sandro; Marafetti, Claudio

2016-01-01

OBIETTIVI: descrivere, nella ASL 21 di Legnago (VR), l'andamento di alcuni indicatori sanitari tra il 2009, anno precedente all'avvio di un progetto triennale per la gestione integrata dell'assistenza al paziente con diabete mellito di tipo 2, e il 2012, ultimo anno del progetto. DISEGNO: studio longitudinale trasversale ripetuto. SETTING E PARTECIPANTI: tutti i pazienti diabetici di tipo 2 della ASL 21, identificati nei database aziendali (in base a esenzioni per patologia, accessi al servizio diabetologico, consumo di farmaci antidiabetici e strisce per la determinazione della glicemia) e nelle cartelle cliniche dei medici di famiglia. PRINCIPALI MISURE DI OUTCOME: numero di test diagnostici e di follow-up erogati, consumo di farmaci, prestazioni specialistiche, accessi al pronto soccorso, ricoveri e mortalità. RISULTATI: nonostante un calo generalizzato (-3,1%) nei test erogati dalla ASL 21 ai suoi assistititi nel periodo 2009-2012, l'analisi ha documentato un marcato aumento per gli esami previsti nella gestione del diabete, quali curve da carico glicemico (+104,3%), emoglobina glicata (+19,0%) e microalbuminuria (+296,1%). I soggetti identificati come diabetici sono aumentati da 8.084 nel 2009 (5,2%) a 9.221 nel 2012 (5,9%). Sono stati osservati aumenti nella prevalenza di pazienti visitati presso un servizio diabetologico (dal 22,6% al 39,0%), nonché negli utilizzatori di metformina (dal 28,0% al 37,5%), insuline (dal 13,5% al 18,3%) e incretine (dall'1,4% al 9,0%). Il consumo di sulfaniluree è, invece, calato (dal 49,9% al 40,8%), come anche l'erogazione di alcune prestazioni specialistiche, gli accessi al pronto soccorso e i ricoveri, mentre il tasso di mortalità è rimasto stabile (29,6 decessi x1.000/anno). CONCLUSIONE: durante il periodo di implementazione del progetto sembra essersi verificato un aumento della sensibilità diagnostica e una maggiore presa in carico del paziente diabetico. Anche se la natura osservazionale dello studio non consente di dimostrare una relazione causa-effetto, i risultati sembrano supportare l'ipotesi che la gestione integrata della patologia migliori l'appropriatezza dell'assistenza.

A content analysis of outdoor non-alcoholic beverage advertisements in Ghana.

PubMed

Bragg, Marie A; Hardoby, Tamara; Pandit, Natasha G; Raji, Yemi R; Ogedegbe, Gbenga

2017-06-06

This was a two-part descriptive study designed to (1) assess the marketing themes and sugar content of beverages promoted in outdoor advertisements (ads) within a portion of Accra, Ghana and (2) quantify the types of ads that appeared along the Accra-Cape Coast Highway. A 4.7 km 2 area of Accra, Ghana and a 151 km region along the highway represented the target areas for collecting photos of outdoor beverage ads. Number and types of beverage ads, sugar content of beverage products featured in ads and marketing themes used in ads. Two researchers photographed outdoor beverage ads in a 4.7 km 2 area of Accra and used content analysis to assess marketing themes of ads, including the portrayal of children, local culture, music, sports and health. Researchers also recorded the number and type of ads along a 151 km stretch of the Accra-Cape Coast Highway. Researchers assessed the added sugar content to determine which beverages were sugar-sweetened beverages (SSBs). Seventy-seven photographed ads were analysed. Seventy-three per cent (72.7%) of ads featured SSBs, and Coca-Cola accounted for 59.7% of ads. Sixty-five per cent (64.9%) of all ads featured sodas, while 35.1% advertised energy drinks, bottled or canned juice drinks and coffee-based, milk-based and water-based beverages. Thirteen per cent (13%) of ads featured children and 5.2% were located near schools or playgrounds. Nine per cent (9.1%) of ads contained a reference to health and 7.8% contained a reference to fitness/strength/sport. Along the Accra-Cape Coast Highway, Coca-Cola accounted for 60% of branded ads. This study demonstrates the frequency of outdoor SSB ads within a 4.7 km 2 area of Accra, Ghana. Coca-Cola was featured in the majority of ads, and the child-targeted nature of some ads indicates a need to expand the Children's Food and Beverage Advertising Initiative pledge to reduce child-targeted marketing on a global scale. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A content analysis of outdoor non-alcoholic beverage advertisements in Ghana

PubMed Central

Bragg, Marie A; Hardoby, Tamara; Pandit, Natasha G; Raji, Yemi R; Ogedegbe, Gbenga

2017-01-01

Objectives This was a two-part descriptive study designed to (1) assess the marketing themes and sugar content of beverages promoted in outdoor advertisements (ads) within a portion of Accra, Ghana and (2) quantify the types of ads that appeared along the Accra-Cape Coast Highway. Setting A 4.7 km2 area of Accra, Ghana and a 151 km region along the highway represented the target areas for collecting photos of outdoor beverage ads. Primary and secondary outcome measures Number and types of beverage ads, sugar content of beverage products featured in ads and marketing themes used in ads. Design Two researchers photographed outdoor beverage ads in a 4.7 km2 area of Accra and used content analysis to assess marketing themes of ads, including the portrayal of children, local culture, music, sports and health. Researchers also recorded the number and type of ads along a 151 km stretch of the Accra-Cape Coast Highway. Researchers assessed the added sugar content to determine which beverages were sugar-sweetened beverages (SSBs). Results Seventy-seven photographed ads were analysed. Seventy-three per cent (72.7%) of ads featured SSBs, and Coca-Cola accounted for 59.7% of ads. Sixty-five per cent (64.9%) of all ads featured sodas, while 35.1% advertised energy drinks, bottled or canned juice drinks and coffee-based, milk-based and water-based beverages. Thirteen per cent (13%) of ads featured children and 5.2% were located near schools or playgrounds. Nine per cent (9.1%) of ads contained a reference to health and 7.8% contained a reference to fitness/strength/sport. Along the Accra-Cape Coast Highway, Coca-Cola accounted for 60% of branded ads. Conclusion This study demonstrates the frequency of outdoor SSB ads within a 4.7 km2 area of Accra, Ghana. Coca-Cola was featured in the majority of ads, and the child-targeted nature of some ads indicates a need to expand the Children’s Food and Beverage Advertising Initiative pledge to reduce child-targeted marketing on a global scale. PMID:28588104

Hybrid Packet-Pheromone-Based Probabilistic Routing for Mobile Ad Hoc Networks

NASA Astrophysics Data System (ADS)

Kashkouli Nejad, Keyvan; Shawish, Ahmed; Jiang, Xiaohong; Horiguchi, Susumu

Ad-Hoc networks are collections of mobile nodes communicating using wireless media without any fixed infrastructure. Minimal configuration and quick deployment make Ad-Hoc networks suitable for emergency situations like natural disasters or military conflicts. The current Ad-Hoc networks can only support either high mobility or high transmission rate at a time because they employ static approaches in their routing schemes. However, due to the continuous expansion of the Ad-Hoc network size, node-mobility and transmission rate, the development of new adaptive and dynamic routing schemes has become crucial. In this paper we propose a new routing scheme to support high transmission rates and high node-mobility simultaneously in a big Ad-Hoc network, by combining a new proposed packet-pheromone-based approach with the Hint Based Probabilistic Protocol (HBPP) for congestion avoidance with dynamic path selection in packet forwarding process. Because of using the available feedback information, the proposed algorithm does not introduce any additional overhead. The extensive simulation-based analysis conducted in this paper indicates that the proposed algorithm offers small packet-latency and achieves a significantly higher delivery probability in comparison with the available Hint-Based Probabilistic Protocol (HBPP).

Non-motor tasks improve adaptive brain-computer interface performance in users with severe motor impairment

PubMed Central

Faller, Josef; Scherer, Reinhold; Friedrich, Elisabeth V. C.; Costa, Ursula; Opisso, Eloy; Medina, Josep; Müller-Putz, Gernot R.

2014-01-01

Individuals with severe motor impairment can use event-related desynchronization (ERD) based BCIs as assistive technology. Auto-calibrating and adaptive ERD-based BCIs that users control with motor imagery tasks (“SMR-AdBCI”) have proven effective for healthy users. We aim to find an improved configuration of such an adaptive ERD-based BCI for individuals with severe motor impairment as a result of spinal cord injury (SCI) or stroke. We hypothesized that an adaptive ERD-based BCI, that automatically selects a user specific class-combination from motor-related and non motor-related mental tasks during initial auto-calibration (“Auto-AdBCI”) could allow for higher control performance than a conventional SMR-AdBCI. To answer this question we performed offline analyses on two sessions (21 data sets total) of cue-guided, five-class electroencephalography (EEG) data recorded from individuals with SCI or stroke. On data from the twelve individuals in Session 1, we first identified three bipolar derivations for the SMR-AdBCI. In a similar way, we determined three bipolar derivations and four mental tasks for the Auto-AdBCI. We then simulated both, the SMR-AdBCI and the Auto-AdBCI configuration on the unseen data from the nine participants in Session 2 and compared the results. On the unseen data of Session 2 from individuals with SCI or stroke, we found that automatically selecting a user specific class-combination from motor-related and non motor-related mental tasks during initial auto-calibration (Auto-AdBCI) significantly (p < 0.01) improved classification performance compared to an adaptive ERD-based BCI that only used motor imagery tasks (SMR-AdBCI; average accuracy of 75.7 vs. 66.3%). PMID:25368546

Combination recombinant simian or chimpanzee adenoviral vectors for vaccine development.

PubMed

Cheng, Cheng; Wang, Lingshu; Ko, Sung-Youl; Kong, Wing-Pui; Schmidt, Stephen D; Gall, Jason G D; Colloca, Stefano; Seder, Robert A; Mascola, John R; Nabel, Gary J

2015-12-16

Recombinant adenoviral vector (rAd)-based vaccines are currently being developed for several infectious diseases and cancer therapy, but pre-existing seroprevalence to such vectors may prevent their use in broad human populations. In this study, we investigated the potential of low seroprevalence non-human primate rAd vectors to stimulate cellular and humoral responses using HIV/SIV Env glycoprotein (gp) as the representative antigen. Mice were immunized with novel simian or chimpanzee rAd (rSAV or rChAd) vectors encoding HIV gp or SIV gp by single immunization or in heterologous prime/boost combinations (DNA/rAd; rAd/rAd; rAd/NYVAC or rAd/rLCM), and adaptive immunity was assessed. Among the rSAV and rChAd tested, rSAV16 or rChAd3 vector alone generated the most potent immune responses. The DNA/rSAV regimen also generated immune responses similar to the DNA/rAd5 regimen. rChAd63/rChAd3 and rChAd3 /NYVAC induced similar or even higher levels of CD4+ and CD8+ T-cell and IgG responses as compared to rAd28/rAd5, one of the most potent combinations of human rAds. The optimized vaccine regimen stimulated improved cellular immune responses and neutralizing antibodies against HIV compared to the DNA/rAd5 regimen. Based on these results, this type of novel rAd vector and its prime/boost combination regimens represent promising candidates for vaccine development. Published by Elsevier Ltd.

Adenovirus vector-induced immune responses in nonhuman primates: responses to prime boost regimens.

PubMed

Tatsis, Nia; Lasaro, Marcio O; Lin, Shih-Wen; Haut, Larissa H; Xiang, Zhi Q; Zhou, Dongming; Dimenna, Lauren; Li, Hua; Bian, Ang; Abdulla, Sarah; Li, Yan; Giles-Davis, Wynetta; Engram, Jessica; Ratcliffe, Sarah J; Silvestri, Guido; Ertl, Hildegund C; Betts, Michael R

2009-05-15

In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with preexisting neutralizing Abs against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here, we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee-derived Ad vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the chimpanzee-derived Ad vectors induced higher T and B cell responses than did repeated immunizations with the AdHu5 vector, especially in AdHu5-preexposed macaques.

An evaluation of volume-based morphometry for prediction of mild cognitive impairment and Alzheimer's disease

PubMed Central

Schmitter, Daniel; Roche, Alexis; Maréchal, Bénédicte; Ribes, Delphine; Abdulkadir, Ahmed; Bach-Cuadra, Meritxell; Daducci, Alessandro; Granziera, Cristina; Klöppel, Stefan; Maeder, Philippe; Meuli, Reto; Krueger, Gunnar

2014-01-01

Voxel-based morphometry from conventional T1-weighted images has proved effective to quantify Alzheimer's disease (AD) related brain atrophy and to enable fairly accurate automated classification of AD patients, mild cognitive impaired patients (MCI) and elderly controls. Little is known, however, about the classification power of volume-based morphometry, where features of interest consist of a few brain structure volumes (e.g. hippocampi, lobes, ventricles) as opposed to hundreds of thousands of voxel-wise gray matter concentrations. In this work, we experimentally evaluate two distinct volume-based morphometry algorithms (FreeSurfer and an in-house algorithm called MorphoBox) for automatic disease classification on a standardized data set from the Alzheimer's Disease Neuroimaging Initiative. Results indicate that both algorithms achieve classification accuracy comparable to the conventional whole-brain voxel-based morphometry pipeline using SPM for AD vs elderly controls and MCI vs controls, and higher accuracy for classification of AD vs MCI and early vs late AD converters, thereby demonstrating the potential of volume-based morphometry to assist diagnosis of mild cognitive impairment and Alzheimer's disease. PMID:25429357

Value Added Based on Educational Positions in Dutch Secondary Education

ERIC Educational Resources Information Center

Timmermans, Anneke C.; Bosker, Roel J.; de Wolf, Inge F.; Doolaard, Simone; van der Werf, Margaretha P. C.

2014-01-01

Estimating added value as an indicator of school effectiveness in the context of educational accountability often occurs using test or examination scores of students. This study investigates the possibilities for using scores of educational positions as an alternative indicator. A number of advantages of a value added indicator based on…

Computer-aided diagnostic method for classification of Alzheimer's disease with atrophic image features on MR images

NASA Astrophysics Data System (ADS)

Arimura, Hidetaka; Yoshiura, Takashi; Kumazawa, Seiji; Tanaka, Kazuhiro; Koga, Hiroshi; Mihara, Futoshi; Honda, Hiroshi; Sakai, Shuji; Toyofuku, Fukai; Higashida, Yoshiharu

2008-03-01

Our goal for this study was to attempt to develop a computer-aided diagnostic (CAD) method for classification of Alzheimer's disease (AD) with atrophic image features derived from specific anatomical regions in three-dimensional (3-D) T1-weighted magnetic resonance (MR) images. Specific regions related to the cerebral atrophy of AD were white matter and gray matter regions, and CSF regions in this study. Cerebral cortical gray matter regions were determined by extracting a brain and white matter regions based on a level set based method, whose speed function depended on gradient vectors in an original image and pixel values in grown regions. The CSF regions in cerebral sulci and lateral ventricles were extracted by wrapping the brain tightly with a zero level set determined from a level set function. Volumes of the specific regions and the cortical thickness were determined as atrophic image features. Average cortical thickness was calculated in 32 subregions, which were obtained by dividing each brain region. Finally, AD patients were classified by using a support vector machine, which was trained by the image features of AD and non-AD cases. We applied our CAD method to MR images of whole brains obtained from 29 clinically diagnosed AD cases and 25 non-AD cases. As a result, the area under a receiver operating characteristic (ROC) curve obtained by our computerized method was 0.901 based on a leave-one-out test in identification of AD cases among 54 cases including 8 AD patients at early stages. The accuracy for discrimination between 29 AD patients and 25 non-AD subjects was 0.840, which was determined at the point where the sensitivity was the same as the specificity on the ROC curve. This result showed that our CAD method based on atrophic image features may be promising for detecting AD patients by using 3-D MR images.

Adenovirus vector-induced immune responses in nonhuman primates: responses to prime boost regimens1

PubMed Central

Tatsis, Nia; Lasaro, Marcio O.; Lin, Shih-Wen; Xiang, Zhi Q.; Zhou, Dongming; DiMenna, Lauren; Li, Hua; Bian, Ang; Abdulla, Sarah; Li, Yan; Giles-Davis, Wynetta; Engram, Jessica; Ratcliffe, Sarah J.; Silvestri, Guido; Ertl, Hildegund C.; Betts, Michael R.

2009-01-01

In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with pre-existing neutralizing antibodies against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee derived Ad (AdC) vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the AdC vectors induced higher T and B cell responses than repeated immunizations with the AdHu5 vector especially in AdHu5-pre-exposed macaques. PMID:19414814

BrGDGT-based quantitative temperature reconstruction over the past 2000 years from an alpine lake in subtropical southwestern China

NASA Astrophysics Data System (ADS)

Zhao, C.; Feng, X.

2017-12-01

BrGDGTs have been proposed as a proxy for quantitative paleotemperature reconstructions in terrestrial environment, and numerous transfer functions have been framed based on modern soils and lake sediments. However, these spatial-based functions have been seldom successful for paleotemperature reconstructions in lake sediments. In this study, we report a quantitative temperature record over the past 2000 years, using a temporal-based transfer function inferred from branched GDGTs from a sediment core collected at a small alpine lake (Tiancai lake, 26°38'E, 99°43'N, 3898 m asl) in a remote location in subtropical southwestern China. The chronology is established by both 210Pb and AMS-14C dating methods. We find a significant correlation between brGDGT distributions and instrumental mean annual air temperature (MAAT) (R2=0.902, p<0.0001) over the past 60 years. We then establish a local instrumental calibration and apply it to the entire core for MAAT reconstruction over the past 2000 years. Our preliminary results show the reconstructed MAAT varies between -0.77 and 4.13° over the past 2000 years. Our data indicate four warm intervals at 20-142AD, 321-578AD, 796-1215AD and after 1940AD, and four cold intervals at 158-321AD, 550-657AD, 1500-1727AD, 1810-1912AD. The warm period at 796-1215AD and the cold period at 1500-1727AD are likely corresponding with the Medieval Climate Anomaly (MCA) and the Little Ice Age (LIA), respectively, which is consistent with published data in northern China and the northern Hemisphere. Our preliminary result indicates that this temporal-based calibration could be more practical in some environmental-stable open lakes, and also suggests coherent temperature changes in the subtropical and high-latitude northern hemisphere over the past 2000 years.

Application of probabilistically weighted graphs to image-based diagnosis of Alzheimer's disease using diffusion MRI

NASA Astrophysics Data System (ADS)

Maryam, Syeda; McCrackin, Laura; Crowley, Mark; Rathi, Yogesh; Michailovich, Oleg

2017-03-01

The world's aging population has given rise to an increasing awareness towards neurodegenerative disorders, including Alzheimers Disease (AD). Treatment options for AD are currently limited, but it is believed that future success depends on our ability to detect the onset of the disease in its early stages. The most frequently used tools for this include neuropsychological assessments, along with genetic, proteomic, and image-based diagnosis. Recently, the applicability of Diffusion Magnetic Resonance Imaging (dMRI) analysis for early diagnosis of AD has also been reported. The sensitivity of dMRI to the microstructural organization of cerebral tissue makes it particularly well-suited to detecting changes which are known to occur in the early stages of AD. Existing dMRI approaches can be divided into two broad categories: region-based and tract-based. In this work, we propose a new approach, which extends region-based approaches to the simultaneous characterization of multiple brain regions. Given a predefined set of features derived from dMRI data, we compute the probabilistic distances between different brain regions and treat the resulting connectivity pattern as an undirected, fully-connected graph. The characteristics of this graph are then used as markers to discriminate between AD subjects and normal controls (NC). Although in this preliminary work we omit subjects in the prodromal stage of AD, mild cognitive impairment (MCI), our method demonstrates perfect separability between AD and NC subject groups with substantial margin, and thus holds promise for fine-grained stratification of NC, MCI and AD populations.

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model

PubMed Central

2010-01-01

Background Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. Methods A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age ≥55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. Results The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). Conclusions This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials. PMID:20433705

Modeling screening, prevention, and delaying of Alzheimer's disease: an early-stage decision analytic model.

PubMed

Furiak, Nicolas M; Klein, Robert W; Kahle-Wrobleski, Kristin; Siemers, Eric R; Sarpong, Eric; Klein, Timothy M

2010-04-30

Alzheimer's Disease (AD) affects a growing proportion of the population each year. Novel therapies on the horizon may slow the progress of AD symptoms and avoid cases altogether. Initiating treatment for the underlying pathology of AD would ideally be based on biomarker screening tools identifying pre-symptomatic individuals. Early-stage modeling provides estimates of potential outcomes and informs policy development. A time-to-event (TTE) simulation provided estimates of screening asymptomatic patients in the general population age > or =55 and treatment impact on the number of patients reaching AD. Patients were followed from AD screen until all-cause death. Baseline sensitivity and specificity were 0.87 and 0.78, with treatment on positive screen. Treatment slowed progression by 50%. Events were scheduled using literature-based age-dependent incidences of AD and death. The base case results indicated increased AD free years (AD-FYs) through delays in onset and a reduction of 20 AD cases per 1000 screened individuals. Patients completely avoiding AD accounted for 61% of the incremental AD-FYs gained. Total years of treatment per 1000 screened patients was 2,611. The number-needed-to-screen was 51 and the number-needed-to-treat was 12 to avoid one case of AD. One-way sensitivity analysis indicated that duration of screening sensitivity and rescreen interval impact AD-FYs the most. A two-way sensitivity analysis found that for a test with an extended duration of sensitivity (15 years) the number of AD cases avoided was 6,000-7,000 cases for a test with higher sensitivity and specificity (0.90,0.90). This study yielded valuable parameter range estimates at an early stage in the study of screening for AD. Analysis identified duration of screening sensitivity as a key variable that may be unavailable from clinical trials.

Neutralized adenovirus-immune complexes can mediate effective gene transfer via an Fc receptor-dependent infection pathway.

PubMed

Leopold, Philip L; Wendland, Rebecca L; Vincent, Theresa; Crystal, Ronald G

2006-10-01

Neutralization of adenovirus (Ad) by anti-Ad neutralizing antibodies in serum involves formation of Ad-immune complexes that prevent the virus from interacting with target cells. We hypothesized that Ad-immune complexes likely contain viable Ad vectors which, although no longer capable of gaining access to receptors on target cells, may be able to express transgenes in cells bearing Fc receptors for immunoglobulins, i.e., that antibody-based "neutralization" of Ad vectors may be circumvented by the Fc receptor pathway. To test this hypothesis, we expressed the Fcgamma receptor IIA (FcgammaR) in A549 lung epithelial cells or human dermal fibroblasts and evaluated gene transfer in the presence of human neutralizing anti-Ad serum. FcgammaR-expressing cells bound and internalized copious amounts of Ad, with a distinct population of internalized Ad trafficking to the nucleus. The dose-response curves for inhibition of gene transfer revealed that FcgammaR-expressing cells required a more-than-10-fold higher concentration of anti-Ad serum to achieve 50% inhibition of Ad-encoded beta-galactosidase expression compared with non-FcgammaR-expressing cells. The discrepancy between neutralization of Ad during infection of FcgammaR-expressing cells and neutralization of Ad during infection of non-FcgammaR-expressing cells occurred with either heat-inactivated or non-heat-inactivated sera, was blocked by addition of purified Fc domain protein, and did not require the cytoplasmic domain of FcgammaR, suggesting that immune complex internalization proceeded via endocytosis rather than phagocytosis. FcgammaR-mediated infection by Ad-immune complexes did not require expression of the coxsackie virus-Ad receptor (CAR) since similar data were obtained when CAR-deficient human dermal fibroblasts were engineered to express FcgammaR. However, interaction of the Ad penton base with cell surface integrins contributed to the difference in neutralization between FcgammaR-expressing and non-FcgammaR-expressing cells. The data indicate that complexes formed from Ad and anti-Ad neutralizing antibodies, while compromised with respect to infection of non-FcgammaR-expressing target cells, maintain the potential to transfer genes to FcgammaR-expressing cells, with consequent expression of the transgene. The formation of Ad-immune complexes that can target viable virus to antigen-presenting cells may account for the success of Ad-based vaccines administered in the presence of low levels of neutralizing anti-Ad antibody.

Association of Alzheimer's disease GWAS loci with MRI markers of brain aging.

PubMed

Chauhan, Ganesh; Adams, Hieab H H; Bis, Joshua C; Weinstein, Galit; Yu, Lei; Töglhofer, Anna Maria; Smith, Albert Vernon; van der Lee, Sven J; Gottesman, Rebecca F; Thomson, Russell; Wang, Jing; Yang, Qiong; Niessen, Wiro J; Lopez, Oscar L; Becker, James T; Phan, Thanh G; Beare, Richard J; Arfanakis, Konstantinos; Fleischman, Debra; Vernooij, Meike W; Mazoyer, Bernard; Schmidt, Helena; Srikanth, Velandai; Knopman, David S; Jack, Clifford R; Amouyel, Philippe; Hofman, Albert; DeCarli, Charles; Tzourio, Christophe; van Duijn, Cornelia M; Bennett, David A; Schmidt, Reinhold; Longstreth, William T; Mosley, Thomas H; Fornage, Myriam; Launer, Lenore J; Seshadri, Sudha; Ikram, M Arfan; Debette, Stephanie

2015-04-01

Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons. Copyright © 2015 Elsevier Inc. All rights reserved.

Qualitative or Quantitative Differences between Asperger's Disorder and Autism? Historical Considerations

ERIC Educational Resources Information Center

Sanders, James Ladell

2009-01-01

The histories of autism and Asperger's Disorder (AD), based on original contributions by Kanner and Asperger, are reviewed in relation to DSM-IV diagnostic criteria. Their original articles appear to have influenced the distinction between AD and autism made in the DSM-IV. Based on up-to-date empirical research, however, it appears that AD and…

A UPLC-TOF/MS-based metabolomics study of rattan stems of Schisandra chinensis effects on Alzheimer's disease rats model.

PubMed

Yang, Bing-You; Tan, Jin-Yan; Liu, Yan; Liu, Bo; Jin, Shuang; Guo, Hong-Wei; Kuang, Hai-Xue

2018-02-01

A UPLC-TOF/MS-based metabolomics method was established to explore the therapeutic mechanisms of rattan stems of S. chinensis (SCS) in Alzheimer's disease (AD). Experimental AD model was induced by intra-hippocampal Aβ 1-42 injection in rats. Cognitive function and oxidative stress condition in brain of AD rats were assessed using Morris water maze tests and antioxidant assays [malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)], respectively. UPLC-TOF/MS combined with multivariate statistical analysis were conducted to study the changes in metabolic networks in serum of rats. The results indicated that the AD model was established successfully and the inducement of Aβ 1-42 caused a decline in spatial learning and memory of rats. The injection of Aβ 1-42 in rat brains significantly elevated the level of MDA, and reduced SOD and GSH-Px activities. In addition, SCS showed significant anti-AD effects on model rats. A total of 30 metabolites were finally identified as potential biomarkers of AD and 14 of them had a significant recovery compared with the AD model after SCS administration. Changes in AD metabolite profiling were restored to different levels through the regulation of 13 pathways. This is first report on the use of the UPLC-TOF/MS-based serum metabolomics method to investigate therapeutic effects of SCS on AD, and enrich potential biomarkers and metabolic networks of AD. Copyright © 2017 John Wiley & Sons, Ltd.

Advertisement scheduling on commercial radio station using genetics algorithm

NASA Astrophysics Data System (ADS)

Purnamawati, S.; Nababan, E. B.; Tsani, B.; Taqyuddin, R.; Rahmat, R. F.

2018-03-01

On the commercial radio station, the advertising schedule is done manually, which resulted in ineffectiveness of ads schedule. Playback time consists of two types such as prime time and regular time. Radio Ads scheduling will be discussed in this research is based on ad playback schedule between 5am until 12am which rules every 15 minutes. It provides 3 slots ads with playback duration per ads maximum is 1 minute. If the radio broadcast time per day is 12 hours, then the maximum number of ads per day which can be aired is 76 ads. The other is the enactment of rules of prime time, namely the hours where the common people (listeners) have the greatest opportunity to listen to the radio, namely between the hours and hours of 4 am - 8 am, 6 pm - 10 pm. The number of screenings of the same ads on one day are limited to prime time ie 5 times, while for regular time is 8 times. Radio scheduling process is done using genetic algorithms which are composed of processes initialization chromosomes, selection, crossover and mutation. Study on chromosome 3 genes, each chromosome will be evaluated based on the value of fitness calculated based on the number of infractions that occurred on each individual chromosome. Where rule 1 is the number of screenings per ads must not be more than 5 times per day and rule 2 is there should never be two or more scheduling ads delivered on the same day and time. After fitness value of each chromosome is acquired, then the do the selection, crossover and mutation. From this research result, the optimal advertising schedule with schedule a whole day and ads data playback time ads with this level of accuracy: the average percentage was 83.79%.

Identification and medical utilization of incident cases of alcohol dependence: A population-based case-control study.

PubMed

Pan, Chun-Hung; Li, Min-Shan; Yang, Tien-Wey; Huang, Ming-Chyi; Su, Sheng-Shiang; Hung, Yen-Ni; Chen, Chiao-Chicy; Kuo, Chian-Jue

2018-05-05

Patients with alcohol dependence (AD) often seek help from medical professionals due to alcohol-related diseases, but the overall distribution of medical specialties identifying new AD cases is unclear. We investigated how such cases were identified and how medical resources were utilized before the identification of AD in a nationwide cohort. We enrolled a population-based cohort (N = 1,000,000) using the National Health Insurance Research Database of Taiwan; 8181 cases with incident AD were retrieved between January 1, 2000, and December 31, 2010. For this nested case-control study, four controls were matched for age and sex with each case based on risk-set sampling. We measured various dimensions of medical utilization before AD was diagnosed, including department visited, physical comorbidity, and medication used. Conditional logistic regression was used for estimating the variables associated with AD. Patients living in less urbanized areas who were unemployed were more likely to develop AD. The highest proportions (34.2%) of AD cases were identified in the internal medicine department, followed by the emergency (22.3%) and psychiatry (18.7%) departments. AD patients had a higher risk of comorbid chronic hepatic disease (adjusted RR = 2.72, p < 0.001) before identification of AD than controls. AD patients also had greater numbers of hospital admissions than controls, including non-psychiatric and psychiatric hospitalizations. Outpatient visit numbers were similar for AD patients and controls. The findings indicate that clinicians providing care in diverse medical settings should be prepared to screen for unhealthy alcohol use and to mitigate its detrimental effects. Copyright © 2018 Elsevier B.V. All rights reserved.

Next-Generation A/D Sampler ADS3000+ for VLBI2010

NASA Technical Reports Server (NTRS)

Takefuji, Kazuhiro; Takeuchi, Hiroshi; Tsutsumi, Masanori; Koyama, Yasuhiro

2010-01-01

A high-speed A/D sampler, called ADS3000+, has been developed in 2008, which can sample one analog signal up to 4 Gbps to versatile Linux PC. After A/D conversion, the ADS3000+ can perform digital signal processing such as real-time DBBC (Digital Base Band Conversion) and FIR filtering such as simple CW RFI filtering using the installed FPGAs. A 4 Gsps fringe test with the ADS3000+ has been successfully performed. The ADS3000+ will not exclusively be used for VLBI but will also be employed in other applications.

Balloon-borne air traffic management (ATM) as a precursor to space-based ATM

NASA Astrophysics Data System (ADS)

Brodsky, Yuval; Rieber, Richard; Nordheim, Tom

2012-01-01

The International Space University—Balloon Air traffic control Technology Experiment (I-BATE ) has flown on board two stratospheric balloons and has tracked nearby aircraft by receiving their Automatic Dependent Surveillance-Broadcast (ADS-B) transmissions. Air traffic worldwide is facing increasing congestion. It is predicted that daily European flight volumes will more than double by 2030 compared to 2009 volumes. ADS-B is an air traffic management system being used to mitigate air traffic congestion. Each aircraft is equipped with both a GPS receiver and an ADS-B transponder. The transponder transmits an equipped aircraft's unique identifier, position, heading, and velocity once per second. The ADS-B transmissions can then be received by ground stations for use in traditional air traffic management. Airspace not monitored by these ground stations or other traditional means remains uncontrolled and poorly monitored. A constellation of space-based ADS-B receivers could close these gaps and provide global air traffic monitoring. By flying an ADS-B receiver on a stratospheric balloon, I-BATE has served as a precursor to a constellation of ADS-B-equipped Earth-orbiting satellites. From the ˜30 km balloon altitude, I-BATE tracked aircraft ranging up to 850 km. The experiment has served as a proof of concept for space-based air traffic management and supports a technology readiness level 6 of space-based ADS-B reception. I-BATE: International Space University—Balloon Air traffic control Technology Experiment.

Study of the Usability of Spaced Retrieval Exercise Using Mobile Devices for Alzheimer’s Disease Rehabilitation

PubMed Central

Mowafi, Yaser; Mashal, Ehab

2014-01-01

Background Alzheimer's disease (AD) is an irreversible brain disease that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest daily tasks. Recent studies showed that people with AD might actually benefit from physical exercises and rehabilitation processes. Studies show that rehabilitation would also add value in making the day for an individual with AD a little less foggy, frustrating, isolated, and stressful for as long as possible. Objective The focus of our work was to explore the use of modern mobile technology to enable people with AD to improve their abilities to perform activities of daily living, and hence to promote independence and participation in social activities. Our work also aimed at reducing the burden on caregivers by increasing the AD patients’ sense of competence and ability to handle behavior problems. Methods We developed ADcope, an integrated app that includes several modules that targeted individuals with AD, using mobile devices. We have developed two different user interfaces: text-based and graphic-based. To evaluate the usability of the app, 10 participants with early stages of AD were asked to run the two user interfaces of the spaced retrieval memory exercise using a tablet mobile device. Results We selected 10 participants with early stages of AD (average age: 75 years; 6/10, 60% males, 4/10, 40% females). The average elapsed time per question between the text-based task (14.04 seconds) and the graphic-based task (12.89 seconds) was significantly different (P=.047). There was also a significant difference (P<.001) between the average correct answer score between the text-based task (7.60/10) and the graphic-based task (8.30/10), and between the text-based task (31.50/100) and the graphic-based task (27.20/100; P<.001). Correlation analysis for the graphic-based task showed that the average elapsed time per question and the workload score were negatively correlated (−.93, and −.79, respectively) to the participants’ performance (P<.001 and P=.006, respectively). Conclusions We found that people with early stages of AD used mobile devices successfully without any prior experience in using such devices. Participants’ measured workload scores were low and posttask satisfaction in fulfilling the required task was conceivable. Results indicate better performance, less workload, and better response time for the graphic-based task compared with the text-based task. PMID:25124077

Satellite single-axis attitude determination based on Automatic Dependent Surveillance - Broadcast signals

NASA Astrophysics Data System (ADS)

Zhou, Kaixing; Sun, Xiucong; Huang, Hai; Wang, Xinsheng; Ren, Guangwei

2017-10-01

The space-based Automatic Dependent Surveillance - Broadcast (ADS-B) is a new technology for air traffic management. The satellite equipped with spaceborne ADS-B system receives the broadcast signals from aircraft and transfers the message to ground stations, so as to extend the coverage area of terrestrial-based ADS-B. In this work, a novel satellite single-axis attitude determination solution based on the ADS-B receiving system is proposed. This solution utilizes the signal-to-noise ratio (SNR) measurement of the broadcast signals from aircraft to determine the boresight orientation of the ADS-B receiving antenna fixed on the satellite. The basic principle of this solution is described. The feasibility study of this new attitude determination solution is implemented, including the link budget and the access analysis. On this basis, the nonlinear least squares estimation based on the Levenberg-Marquardt method is applied to estimate the single-axis orientation. A full digital simulation has been carried out to verify the effectiveness and performance of this solution. Finally, the corresponding results are processed and presented minutely.

Tree-ring-width-based PDSI reconstruction for central Inner Mongolia, China over the past 333 years

NASA Astrophysics Data System (ADS)

Liu, Yu; Zhang, Xinjia; Song, Huiming; Cai, Qiufang; Li, Qiang; Zhao, Boyang; Liu, Han; Mei, Ruochen

2017-02-01

A tree-ring-width chronology was developed from Pinus tabulaeformis aged up to 333 years from central Inner Mongolia, China. The chronology was significantly correlated with the local Palmer Drought Severity Index (PDSI). We therefore reconstructed the first PDSI reconstruction from March to June based on the local tree ring data from 1680 to 2012 AD. The reconstruction explained 40.7 % of the variance (39.7 % after adjusted the degrees of freedom) of the actual PDSI during the calibration period (1951-2012 AD). The reconstructed PDSI series captured the severe drought event of the late 1920s, which occurred extensively in northern China. Running variance analyses indicated that the variability of drought increased sharply after 1960, indicating more drought years, which may imply anthropogenic related global warming effects in the region. In the entire reconstruction, there were five dry periods: 1730-1814 AD, 1849-1869 AD, 1886-1942 AD (including severe drought in late 1920s), 1963-1978 AD and 2004-2007 AD; and five wet periods: 1685-1729 AD, 1815-1848 AD, 1870-1885 AD, 1943-1962 AD and 1979-2003 AD. Conditions turned dry after 2003 AD, and the PDSI from March to June (PDSI36) captured many interannual extreme drought events since then, such as 2005-2008 AD. The reconstruction is comparable to other tree-ring-width-based PDSI series from the neighboring regions, indicating that our reconstruction has good regional representativeness. Significant relationships were found between our PDSI reconstruction and the solar radiation cycle and the sun spot cycle, North Atlantic Oscillation, the El Niño-Southern Oscillation, as well as the Pacific Decadal Oscillation. Power spectral analyses detected 147.0-, 128.2-, 46.5-, 6.5-, 6.3-, 2.6-, 2.2- and 2.0-year quasi-cycles in the reconstructed series.

A physical exercise program using music-supported video-based training in older adults in nursing homes suffering from dementia: a feasibility study.

PubMed

Spildooren, Joke; Speetjens, Ite; Abrahams, Johan; Feys, Peter; Timmermans, Annick

2018-04-28

Motivation towards an exercise program is higher in a small group setting in comparison to individual therapy. Due to attentional problems, group exercises are difficult for people with Alzheimer disease (AD). This study evaluates the feasibility of a music-supported video-based group exercise program in older adults suffering from AD. Five participants with moderate AD were recruited from a nursing home. A progressive physical exercise program using a video-based training with musical accompaniment was performed and digitally recorded to investigate the adherence and performed accuracy of the exercises. The overall participation during the exercises was 84.1%. The quality of the performance was for all exercises above the cut-off scores. A music-supported video-based group exercise program is feasible in persons with AD. The participants were motivated and the expectations towards the program increased over time. Music seemed an important factor for attention in participants with AD.

Osteoporosis in adult patients with atopic dermatitis: A nationwide population-based study

PubMed Central

Lu, Chun-Ching; Su, Yu-Feng; Tsai, Tai-Hsin; Wu, Chieh-Hsin

2017-01-01

The aim of this study was to investigate osteoporosis risk in atopic dermatitis (AD) patients. This study included patients in the Taiwan National Health Insurance Research dataset. The population-based study included all patients aged 20–49 years who had been diagnosed with AD during 1996–2010. In total, 35,229 age and gender-matched patients without AD in a 1:1 ratio were randomly selected as the non-AD group. Cox proportional-hazards regression and Kaplan–Meier analyses were used to measure the hazard ratios and the cumulative incidences of osteoporosis, respectively. During the follow-up period, 360(1.02%) AD patients and 127(0.36%) non-AD patients developed osteoporosis. The overall incidence of osteoporosis was4.72-fold greater in the AD patients compared to the non-AD patients (1.82 vs. 0.24 per 1,000 person-years, respectively) after adjusting for potential confounding factors. Osteoporosis risk factors included female gender, age, advanced Charlson Comorbidity Index, depression and use of corticosteroids. The dataset analysis showed that AD was significantly associated with subsequent risk of osteoporosis. PMID:28207767

Early classification of Alzheimer's disease using hippocampal texture from structural MRI

NASA Astrophysics Data System (ADS)

Zhao, Kun; Ding, Yanhui; Wang, Pan; Dou, Xuejiao; Zhou, Bo; Yao, Hongxiang; An, Ningyu; Zhang, Yongxin; Zhang, Xi; Liu, Yong

2017-03-01

Convergent evidence has been collected to support that Alzheimer's disease (AD) is associated with reduction in hippocampal volume based on anatomical magnetic resonance imaging (MRI) and impaired functional connectivity based on functional MRI. Radiomics texture analysis has been previously successfully used to identify MRI biomarkers of several diseases, including AD, mild cognitive impairment and multiple sclerosis. In this study, our goal was to determine if MRI hippocampal textures, including the intensity, shape, texture and wavelet features, could be served as an MRI biomarker of AD. For this purpose, the texture marker was trained and evaluated from MRI data of 48 AD and 39 normal samples. The result highlights the presence of hippocampal texture abnormalities in AD, and the possibility that texture may serve as a neuroimaging biomarker for AD.

76 FR 1653 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-11

... adding liquidity to the Exchange in NYSE-listed securities, based on an SLP's ADV in added liquidity in... NYSE-listed securities, based on an SLP's ADV in added liquidity in the applicable month. Under the proposal, SLPs that meet the SLP 10% quoting requirement will receive a credit per share per transaction...

Value-Added Dairy Products from Grass-Based Dairy Farms: A Case Study in Vermont

ERIC Educational Resources Information Center

Wang, Qingbin; Parsons, Robert; Colby, Jennifer; Castle, Jeffrey

2016-01-01

On-farm processing of value-added dairy products can be a way for small dairy farms to diversify production and increase revenue. This article examines characteristics of three groups of Vermont farmers who have grass-based dairy farms--those producing value-added dairy products, those interested in such products, and those not interested in such…

Computer-aided classification of patients with dementia of Alzheimer's type based on cerebral blood flow determined with arterial spin labeling technique

NASA Astrophysics Data System (ADS)

Yamashita, Yasuo; Arimura, Hidetaka; Yoshiura, Takashi; Tokunaga, Chiaki; Magome, Taiki; Monji, Akira; Noguchi, Tomoyuki; Toyofuku, Fukai; Oki, Masafumi; Nakamura, Yasuhiko; Honda, Hiroshi

2010-03-01

Arterial spin labeling (ASL) is one of promising non-invasive magnetic resonance (MR) imaging techniques for diagnosis of Alzheimer's disease (AD) by measuring cerebral blood flow (CBF). The aim of this study was to develop a computer-aided classification system for AD patients based on CBFs measured by the ASL technique. The average CBFs in cortical regions were determined as functional image features based on the CBF map image, which was non-linearly transformed to a Talairach brain atlas by using a free-form deformation. An artificial neural network (ANN) was trained with the CBF functional features in 10 cortical regions, and was employed for distinguishing patients with AD from control subjects. For evaluation of the method, we applied the proposed method to 20 cases including ten AD patients and ten control subjects, who were scanned a 3.0-Tesla MR unit. As a result, the area under the receiver operating characteristic curve obtained by the proposed method was 0.893 based on a leave-one-out-by-case test in identification of AD cases among 20 cases. The proposed method would be feasible for classification of patients with AD.

Retrieving atmospheric turbulence information from regular commercial aircraft using Mode-S and ADS-B

NASA Astrophysics Data System (ADS)

Kopeć, Jacek M.; Kwiatkowski, Kamil; de Haan, Siebren; Malinowski, Szymon P.

2016-05-01

Navigational information broadcast by commercial aircraft in the form of Mode-S EHS (Mode-S Enhanced Surveillance) and ADS-B (Automatic Dependent Surveillance-Broadcast) messages can be considered a new source of upper tropospheric and lower stratospheric turbulence estimates. A set of three processing methods is proposed and analysed using a quality record of turbulence encounters made by a research aircraft.The proposed methods are based on processing the vertical acceleration or the background wind into the eddy dissipation rate. Turbulence intensity can be estimated using the standard content of the Mode-S EHS/ADS-B.The results are based on a Mode-S EHS/ADS-B data set generated synthetically based on the transmissions from the research aircraft. This data set was validated using the overlapping record of the Mode-S EHS/ADS-B received from the same research aircraft. The turbulence intensity, meaning the eddy dissipation rate, obtained from the proposed methods based on the Mode-S EHS/ADS-B is compared with the value obtained using on-board accelerometer. The results of the comparison indicate the potential of the methods. The advantages and limitation of the presented approaches are discussed.

Characterization of human adenovirus serotypes 5, 6, 11, and 35 as anticancer agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shashkova, Elena V.; May, Shannon M.; Barry, Michael A., E-mail: mab@mayo.ed

2009-11-25

Human adenovirus type 5 (Ad5) has been the most popular platform for the development of oncolytic Ads. Alternative Ad serotypes with low seroprevalence might allow for improved anticancer efficacy in Ad5-immune patients. We studied the safety and efficacy of rare serotypes Ad6, Ad11 and Ad35. In vitro cytotoxicity of the Ads correlated with expression of CAR and CD46 in most but not all cell lines. Among CAR-binding viruses, Ad5 was often more active than Ad6, among CD46-binding viruses Ad35 was generally more cytotoxic than Ad11 in cell culture studies. Ad5, Ad6, and Ad11 demonstrated similar anticancer activity in vivo, whereasmore » Ad35 was not efficacious. Hepatotoxicity developed only in Ad5-injected mice. Predosing with Ad11 and Ad35 did not increase infection of hepatocytes with Ad5-based vector demonstrating different interaction of these Ads with Kupffer cells. Data obtained in this study suggest developing Ad6 and Ad11 as alternative Ads for anticancer treatment.« less

Phenotypic regional fMRI activation patterns during memory encoding in MCI and AD

PubMed Central

Browndyke, Jeffrey N.; Giovanello, Kelly; Petrella, Jeffrey; Hayden, Kathleen; Chiba-Falek, Ornit; Tucker, Karen A.; Burke, James R.; Welsh-Bohmer, Kathleen A.

2014-01-01

Background Reliable blood-oxygen-level-dependent (BOLD) fMRI phenotypic biomarkers of Alzheimer's disease (AD) or mild cognitive impairment (MCI) are likely to emerge only from a systematic, quantitative, and aggregate examination of the functional neuroimaging research literature. Methods A series of random-effects, activation likelihood estimation (ALE) meta-analyses were conducted on studies of episodic memory encoding operations in AD and MCI samples relative to normal controls. ALE analyses were based upon a thorough literature search for all task-based functional neuroimaging studies in AD and MCI published up to January 2010. Analyses covered 16 fMRI studies, which yielded 144 distinct foci for ALE meta-analysis. Results ALE results indicated several regional task-based BOLD consistencies in MCI and AD patients relative to normal controls across the aggregate BOLD functional neuroimaging research literature. Patients with AD and those at significant risk (MCI) showed statistically significant consistent activation differences during episodic memory encoding in the medial temporal lobe (MTL), specifically parahippocampal gyrus, as well superior frontal gyrus, precuneus, and cuneus, relative to normal controls. Conclusions ALE consistencies broadly support the presence of frontal compensatory activity, MTL activity alteration, and posterior midline “default mode” hyperactivation during episodic memory encoding attempts in the diseased or prospective pre-disease condition. Taken together these robust commonalities may form the foundation for a task-based fMRI phenotype of memory encoding in AD. PMID:22841497

Added sugars: consumption and associated factors among adults and the elderly. São Paulo, Brazil.

PubMed

Bueno, Milena Baptista; Marchioni, Dirce Maria Lobo; César, Chester Luis Galvão; Fisberg, Regina Mara

2012-06-01

To investigate added sugar intake, main dietary sources and factors associated with excessive intake of added sugar. A population-based household survey was carried out in São Paulo, the largest city in Brazil. Cluster sampling was performed and the study sample comprised 689 adults and 622 elderly individuals. Dietary intake was estimated based on a 24-hour food recall. Usual nutrient intake was estimated by correcting for the within-person variance of intake using the Iowa State University (ISU) method. Linear regression analysis was conducted to identify factors associated with added sugar intake. Average of energy intake (EI) from added sugars was 9.1% (95% CI: 8.9%; 9.4%) among adults and 8.4% (95% CI: 8.2%; 8.7%) among the elderly (p < 0.05). Average added sugar intake (% EI) was higher among women than among men (p < 0.05). Soft drink was the main source of added sugar among adults, while table sugar was the main source of added sugar among the elderly. Added sugar intake increased with age among adults. Moreover, higher socioeconomic level was associated with added sugar intake in the same group. Added sugar intake is higher among younger adults of higher socioeconomic level. Soft drink and table sugar accounted for more than 50% of the sugar consumed.

Development of Clinical Vignettes to Describe Alzheimer's Disease Health States: A Qualitative Study

PubMed Central

Oremus, Mark; Xie, Feng; Gaebel, Kathryn

2016-01-01

Aims To develop clinical descriptions (vignettes) of life with Alzheimer’s disease (AD), we conducted focus groups of persons with AD (n = 14), family caregivers of persons with AD (n = 20), and clinicians who see persons with AD in their practices (n = 5). Methods Group participants read existing descriptions of AD and commented on the realism and comprehensibility of the descriptions. We used thematic framework analysis to code the comments into themes and develop three new vignettes to describe mild, moderate, and severe AD. Results Themes included the types of symptoms to mention in the new vignettes, plus the manner in which the vignettes should be written. Since the vignette descriptions were based on focus group participants’ first-hand knowledge of AD, the descriptions can be said to demonstrate content validity. Conclusion Members of the general public can read the vignettes and estimate their health-related quality-of-life (HRQoL) as if they had AD based on the vignette descriptions. This is especially important for economic evaluations of new AD medications, which require HRQoL to be assessed in a manner that persons with AD often find difficult to undertake. The vignettes will allow the general public to serve as a proxy and provide HRQoL estimates in place of persons with AD. PMID:27589604

Metabolomics-based promising candidate biomarkers and pathways in Alzheimer's disease.

PubMed

Kang, Jian; Lu, Jingli; Zhang, Xiaojian

2015-05-01

Pathologically, loss of synapses and neurons, extracellular senile plaques and intracellular neurofibrillary tangles (NFTs) are observed in the brains of patients with Alzheimer's disease (AD). These features are associated with changes Aβ (amyloid β) 40, Aβ42, total tau and phosphorylated tau (p-tau), which are as definitely biomarkers for severe AD state. However, biomarkers for effectively diagnosing AD in the pre-clinical state for directing therapeutic strategies are lacking. Metabolic profiling as a powerful tool to identify new biomarkers is receiving increasing attention in AD. This review will focus on metabolomics-based detection of promising candidate biomarkers and pathways in AD to facilitate the discovery of new medicines and disease pathways.

Developing a Set of Uniform Outcome Measures for Adult Day Services.

PubMed

Anderson, Keith A; Geboy, Lyn; Jarrott, Shannon E; Missaelides, Lydia; Ogletree, Aaron M; Peters-Beumer, Lisa; Zarit, Steven H

2018-06-01

Adult day services (ADS) provide care to adults with physical, functional, and/or cognitive limitations in nonresidential, congregate, community-based settings. ADS programs have emerged as a growing and affordable approach within the home and community-based services sector. Although promising, the growth of ADS has been hampered by a lack of uniform outcome measures and data collection protocols. In this article, the authors detail a recent effort by leading researchers and practitioners in ADS to develop a set of uniform outcome measures. Based upon three recent efforts to develop outcome measures, selection criteria were established and an iterative process was conducted to debate the merits of outcome measures across three domains-participant well-being, caregiver well-being, and health care utilization. The authors conclude by proposing a uniform set of outcome measures to (a) standardize data collection, (b) aid in the development of programming, and (c) facilitate the leveraging of additional funding for ADS.

The Ad5 [E1-, E2b-]-based vector: a new and versatile gene delivery platform

NASA Astrophysics Data System (ADS)

Jones, Frank R.; Gabitzsch, Elizabeth S.; Balint, Joseph P.

2015-05-01

Based upon advances in gene sequencing and construction, it is now possible to identify specific genes or sequences thereof for gene delivery applications. Recombinant adenovirus serotype-5 (Ad5) viral vectors have been utilized in the settings of gene therapy, vaccination, and immunotherapy but have encountered clinical challenges because they are recognized as foreign entities to the host. This recognition leads to an immunologic clearance of the vector that contains the inserted gene of interest and prevents effective immunization(s). We have reported on a new Ad5-based viral vector technology that can be utilized as an immunization modality to induce immune responses even in the presence of Ad5 vector immunity. We have reported successful immunization and immunotherapy results to infectious diseases and cancers. This improved recombinant viral platform (Ad5 [E1-, E2b-]) can now be utilized in the development of multiple vaccines and immunotherapies.

Incidence of Enuresis and Encopresis Among Children with Attention Deficit Hyperactivity Disorder in a Population-Based Birth Cohort

PubMed Central

Mellon, Michael W.; Natchev, Brooke E.; Katusic, Slavica K.; Colligan, Robert C.; Weaver, Amy L.; Voigt, Robert G.; Barbaresi, William J.

2013-01-01

OBJECTIVE This study reports the incidence of enuresis and encopresis among children with attention-deficit/hyperactivity disorder (AD/HD) versus those without AD/HD. METHOD Subjects included 358 (74.5% male) children with research-identified AD/HD from a 1976-1982 population-based birth cohort (N = 5718) and 729 (75.2% male) non-AD/HD control subjects from the same birth cohort, matched by gender and age. All subjects were retrospectively followed from birth until a diagnosis of enuresis or encopresis was made or last follow-up prior to 18 years of age. The complete medical record for each subject was reviewed to obtain information on age of initial diagnosis of an elimination disorder, frequency and duration of symptoms, identification of exclusionary criteria specified by DSM-IV, with confirmation of the diagnosis by expert consensus. RESULTS Children with AD/HD were 2.1 (95% CI, 1.3-3.4; p = 0.002) times more likely to meet DSM-IV criteria for enuresis than non-AD/HD controls; they were 1.8 (95% CI, 1.2 – 2.7; p = 0.006) times more likely to do so than non-AD/HD controls when less stringent criteria for a diagnosis of enuresis were employed. Though not significant, children with AD/HD were 1.8 (95% CI, 0.7-4.6; p = 0.23) times more likely to meet criteria for encopresis than non-AD/HD controls. The relative risk was 2.0 (95% CI, 1.0-4.1; p = 0.05) when a less stringent definition for encopresis was utilized. CONCLUSIONS The results of this population-based study demonstrate that children with AD/HD are more likely than their peers without AD/HD to develop enuresis with a similar trend for encopresis. PMID:23680296

Model-based economic evaluation in Alzheimer's disease: a review of the methods available to model Alzheimer's disease progression.

PubMed

Green, Colin; Shearer, James; Ritchie, Craig W; Zajicek, John P

2011-01-01

To consider the methods available to model Alzheimer's disease (AD) progression over time to inform on the structure and development of model-based evaluations, and the future direction of modelling methods in AD. A systematic search of the health care literature was undertaken to identify methods to model disease progression in AD. Modelling methods are presented in a descriptive review. The literature search identified 42 studies presenting methods or applications of methods to model AD progression over time. The review identified 10 general modelling frameworks available to empirically model the progression of AD as part of a model-based evaluation. Seven of these general models are statistical models predicting progression of AD using a measure of cognitive function. The main concerns with models are on model structure, around the limited characterization of disease progression, and on the use of a limited number of health states to capture events related to disease progression over time. None of the available models have been able to present a comprehensive model of the natural history of AD. Although helpful, there are serious limitations in the methods available to model progression of AD over time. Advances are needed to better model the progression of AD and the effects of the disease on peoples' lives. Recent evidence supports the need for a multivariable approach to the modelling of AD progression, and indicates that a latent variable analytic approach to characterising AD progression is a promising avenue for advances in the statistical development of modelling methods. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

The inclusion of functional connectivity information into fMRI-based neurofeedback improves its efficacy in the reduction of cigarette cravings.

PubMed

Kim, Dong-Youl; Yoo, Seung-Schik; Tegethoff, Marion; Meinlschmidt, Gunther; Lee, Jong-Hwan

2015-08-01

Real-time fMRI (rtfMRI) neurofeedback (NF) facilitates volitional control over brain activity and the modulation of associated mental functions. The NF signals of traditional rtfMRI-NF studies predominantly reflect neuronal activity within ROIs. In this study, we describe a novel rtfMRI-NF approach that includes a functional connectivity (FC) component in the NF signal (FC-added rtfMRI-NF). We estimated the efficacy of the FC-added rtfMRI-NF method by applying it to nicotine-dependent heavy smokers in an effort to reduce cigarette craving. ACC and medial pFC as well as the posterior cingulate cortex and precuneus are associated with cigarette craving and were chosen as ROIs. Fourteen heavy smokers were randomly assigned to receive one of two types of NF: traditional activity-based rtfMRI-NF or FC-added rtfMRI-NF. Participants received rtfMRI-NF training during two separate visits after overnight smoking cessation, and cigarette craving score was assessed. The FC-added rtfMRI-NF resulted in greater neuronal activity and increased FC between the targeted ROIs than the traditional activity-based rtfMRI-NF and resulted in lower craving score. In the FC-added rtfMRI-NF condition, the average of neuronal activity and FC was tightly associated with craving score (Bonferroni-corrected p = .028). However, in the activity-based rtfMRI-NF condition, no association was detected (uncorrected p > .081). Non-rtfMRI data analysis also showed enhanced neuronal activity and FC with FC-added NF than with activity-based NF. These results demonstrate that FC-added rtfMRI-NF facilitates greater volitional control over brain activity and connectivity and greater modulation of mental function than activity-based rtfMRI-NF.

An analysis on Wildland Urban Interface in North Sardinia

NASA Astrophysics Data System (ADS)

Arca, B.; Pellizzaro, G.; Canu, A.; Pintus, G. V.; Ferrara, R.; Duce, P.

2012-04-01

Climate variability and drought, typical of the Mediterranean climate, together with different anthropogenic disturbances (modifications of land use, deforestation, grazing, forest fires, etc.) makes the Mediterranean basin ecosystems extremely sensitive and vulnerable. In the last three decades, an increasing number of fires threatening the wildland urban interface (WUI) was observed. In Sardinia, this phenomenon is particularly evident in tourist and coastal areas where a large number of resorts is built within and surrounded by Mediterranean vegetation that is highly prone to events of wildfire. In these situations, the related risk of damage for villages, tourist resorts, other human activities and people is elevated especially in summer when the presence of human people is highest and meteorological conditions are extreme. In addition, fire can have significant effect on the hydrological response of the WUI causing the intensification of the erosive processes. Therefore, the development of planning policies is required in order to implement strategies to prevent and reduce wildfire and soil erosion risk in wildland urban interface areas. The main aims of this work are i) to assess presence and characteristics of wildland urban interface in a touristic areas of North Sardinia and ii) to evaluate fire danger and soil erosion risk in the studied area. The study was carried out in a coastal area located in North Sardinia, characterized by strong touristic development in the last thirty years. In that area, the characterization and mapping of the WUI were performed. In addition several simulation were carried out by the Farsite fire area simulator with the aim to study the spatial pattern of the fire danger factors in the vegetated areas closer to the WUI. Finally, maps of soil erosion were produced for the identification of the areas at high erosion risk in the WUI. This work is supported by MIIUR - Metodologie e indicatori per la valutazione del rischio di Incendio nelle aree di Interfaccia Urbano Rurale in ambiente mediterraneo. Legge Regionale 7 agosto 2007, n. 7.

ADS pilot program Plan

NASA Technical Reports Server (NTRS)

Clauson, J.; Heuser, J.

1981-01-01

The Applications Data Service (ADS) is a system based on an electronic data communications network which will permit scientists to share the data stored in data bases at universities and at government and private installations. It is designed to allow users to readily locate and access high quality, timely data from multiple sources. The ADS Pilot program objectives and the current plans for accomplishing those objectives are described.

Case-based synthesis in automatic advertising creation system

NASA Astrophysics Data System (ADS)

Zhuang, Yueting; Pan, Yunhe

1995-08-01

Advertising (ads) is an important design area. Though many interactive ad-design softwares have come into commercial use, none of them ever support the intelligent work -- automatic ad creation. The potential for this is enormous. This paper gives a description of our current work in research of an automatic advertising creation system (AACS). After careful analysis of the mental behavior of a human ad designer, we conclude that case-based approach is appropriate to its intelligent modeling. A model for AACS is given in the paper. A case in ads is described as two parts: the creation process and the configuration of the ads picture, with detailed data structures given in the paper. Along with the case representation, we put forward an algorithm. Some issues such as similarity measure computing, and case adaptation have also been discussed.

Gene-based rare allele analysis identified a risk gene of Alzheimer's disease.

PubMed

Kim, Jong Hun; Song, Pamela; Lim, Hyunsun; Lee, Jae-Hyung; Lee, Jun Hong; Park, Sun Ah

2014-01-01

Alzheimer's disease (AD) has a strong propensity to run in families. However, the known risk genes excluding APOE are not clinically useful. In various complex diseases, gene studies have targeted rare alleles for unsolved heritability. Our study aims to elucidate previously unknown risk genes for AD by targeting rare alleles. We used data from five publicly available genetic studies from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the database of Genotypes and Phenotypes (dbGaP). A total of 4,171 cases and 9,358 controls were included. The genotype information of rare alleles was imputed using 1,000 genomes. We performed gene-based analysis of rare alleles (minor allele frequency≤3%). The genome-wide significance level was defined as meta P<1.8×10(-6) (0.05/number of genes in human genome = 0.05/28,517). ZNF628, which is located at chromosome 19q13.42, showed a genome-wide significant association with AD. The association of ZNF628 with AD was not dependent on APOE ε4. APOE and TREM2 were also significantly associated with AD, although not at genome-wide significance levels. Other genes identified by targeting common alleles could not be replicated in our gene-based rare allele analysis. We identified that rare variants in ZNF628 are associated with AD. The protein encoded by ZNF628 is known as a transcription factor. Furthermore, the associations of APOE and TREM2 with AD were highly significant, even in gene-based rare allele analysis, which implies that further deep sequencing of these genes is required in AD heritability studies.

Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice.

PubMed

Tsuji, Takumi; Okuno, Satoshi; Kuroda, Ayano; Hamazaki, Junya; Chikami, Takuma; Sakurai, Sakura; Yoshida, Yuya; Banno, Rie; Fujita, Tetsuro; Kohno, Takeyuki

2016-04-01

The increasing incidence and prevalence of atopic dermatitis (AD) demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of immunomodulator FTY720 ointment (fingolimod) for mite-induced intractable AD using an NC/Nga mouse model. Female NC/Nga mice that developed severe AD were divided into four groups: (1) FTY720 (0.001% FTY720 ointment), (2) tacrolimus (tacrolimus hydrate ointment) (3) betamethasone (betamethasone ointment), and (4) ointment base (hydrophilic petrolatum), all of which received treatment six times per week. Therapeutic efficacy after two weeks was evaluated in terms of AD severity, histochemical observations (epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration), transepidermal water loss (TEWL), and epidermal barrier function (filaggrin expression). Betamethasone treatment showed little effect, confirming that the AD was intractable. In the FTY720 group, AD improved significantly compared with the ointment base group, as did epidermal hypertrophy, mast cell accumulation, and CD3(+) T cell infiltration. In contrast, AD in the tacrolimus and betamethasone groups did not improve significantly, nor did epidermal hypertrophy or mast cell accumulation. Furthermore, in the FTY720 group, TEWL decreased significantly compared with the ointment base group, and filaggrin expression significantly increased compared with the betamethasone and ointment base groups. FTY720 ointment is a promising candidate for treatment of intractable AD. These findings also provide the first evidence that FTY720 ointment ameliorates epidermal barrier function. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Comparison of imaging biomarkers for Alzheimer's disease: amyloid imaging with [18F]florbetapir positron emission tomography and magnetic resonance imaging voxel-based analysis for entorhinal cortex atrophy.

PubMed

Tateno, Amane; Sakayori, Takeshi; Kawashima, Yoshitaka; Higuchi, Makoto; Suhara, Tetsuya; Mizumura, Sunao; Mintun, Mark A; Skovronsky, Daniel M; Honjo, Kazuyoshi; Ishihara, Keiichi; Kumita, Shinichiro; Suzuki, Hidenori; Okubo, Yoshiro

2015-05-01

We compared amyloid positron emission tomography (PET) and magnetic resonance imaging (MRI) in subjects clinically diagnosed with Alzheimer's disease (AD), mild cognitive impairment (MCI), and older healthy controls (OHC) in order to test how these imaging biomarkers represent cognitive decline in AD. Fifteen OHC, 19 patients with MCI, and 19 patients with AD were examined by [(18)F]florbetapir PET to quantify the standard uptake value ratio (SUVR) as the degree of amyloid accumulation, by MRI and the voxel-based specific regional analysis system for AD to calculate z-score as the degree of entorhinal cortex atrophy, and by mini-mental state examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive component--Japanese version (ADAS-Jcog) for cognitive functions. Both cutoff values for measuring AD-like levels of amyloid (1.099 for SUVR) and entorhinal cortex atrophy (1.60 for z-score) were well differentially diagnosed and clinically defined AD from OHC (84.2% for SUVR and 86.7% for z-score). Subgroup analysis based on beta-amyloid positivity revealed that z-score significantly correlated with MMSE (r = -0.626, p < 0.01) and ADAS-Jcog (r = 0.691, p < 0.01) only among subjects with beta-amyloid. This is the first study to compare [(18)F]florbetapir PET and MRI voxel-based analysis of entorhinal cortex atrophy for AD. Both [(18)F]florbetapir PET and MRI detected changes in AD compared with OHC. Considering that entorhinal cortex atrophy correlated well with cognitive decline only among subjects with beta-amyloid, [18F]florbetapir PET makes it possible to detect AD pathology in the early stage, whereas MRI morphometry for subjects with beta-amyloid provides a good biomarker to assess the severity of AD in the later stage. Copyright © 2014 John Wiley & Sons, Ltd.

Simplified and age-appropriate recommendations for added sugars in children.

PubMed

Goran, M I; Riemer, S L; Alderete, T L

2018-04-01

Excess sugar intake increases risk for obesity and related comorbidities among children. The World Health Organization (WHO), American Heart Association (AHA) and the 2015 USDA dietary recommendations have proposed guidelines for added sugar intake to reduce risk for disease. WHO and USDA recommendations are presented as a percentage of daily calories from added sugar. This approach is not easily understood or translated to children, where energy needs increase with age. The AHA recommendation is based on a fixed value of 25 g of added sugar for all children 2-19 years of age. This approach does not take into account the different levels of intake across this wide age range. Due to these limitations, we adapted current recommendations for added sugars based on daily energy needs of children 2-19 years. We used those values to derive simple regression equations to predict grams or teaspoons of added sugars per day based on age that would be equivalent to 10% of daily energy needs. This proposed approach aligns with the changing nutritional needs of children and adolescents during growth. © 2017 World Obesity Federation.

Heterogeneous patterns of brain atrophy in Alzheimer's disease.

PubMed

Poulakis, Konstantinos; Pereira, Joana B; Mecocci, Patrizia; Vellas, Bruno; Tsolaki, Magda; Kłoszewska, Iwona; Soininen, Hilkka; Lovestone, Simon; Simmons, Andrew; Wahlund, Lars-Olof; Westman, Eric

2018-05-01

There is increasing evidence showing that brain atrophy varies between patients with Alzheimer's disease (AD), suggesting that different anatomical patterns might exist within the same disorder. We investigated AD heterogeneity based on cortical and subcortical atrophy patterns in 299 AD subjects from 2 multicenter cohorts. Clusters of patients and important discriminative features were determined using random forest pairwise similarity, multidimensional scaling, and distance-based hierarchical clustering. We discovered 2 typical (72.2%) and 3 atypical (28.8%) subtypes with significantly different demographic, clinical, and cognitive characteristics, and different rates of cognitive decline. In contrast to previous studies, our unsupervised random forest approach based on cortical and subcortical volume measures and their linear and nonlinear interactions revealed more typical AD subtypes with important anatomically discriminative features, while the prevalence of atypical cases was lower. The hippocampal-sparing and typical AD subtypes exhibited worse clinical progression in visuospatial, memory, and executive cognitive functions. Our findings suggest there is substantial heterogeneity in AD that has an impact on how patients function and progress over time. Copyright © 2018 Elsevier Inc. All rights reserved.

Abnormal degree centrality in Alzheimer's disease patients with depression: A resting-state functional magnetic resonance imaging study.

PubMed

Guo, Zhongwei; Liu, Xiaozheng; Hou, Hongtao; Wei, Fuquan; Liu, Jian; Chen, Xingli

2016-06-15

Depression is common in Alzheimer's disease (AD) and occurs in AD patients with a prevalence of up to 40%. It reduces cognitive function and increases the burden on caregivers. Currently, there are very few medications that are useful for treating depression in AD patients. Therefore, understanding the brain abnormalities in AD patients with depression (D-AD) is crucial for developing effective interventions. The aim of this study was to investigate the intrinsic dysconnectivity pattern of whole-brain functional networks at the voxel level in D-AD patients based on degree centrality (DC) as measured by resting-state functional magnetic resonance imaging (R-fMRI). Our study included 32 AD patients. All patients were evaluated using the Neuropsychiatric Inventory and Hamilton Depression Rating Scale and further divided into two groups: 15 D-AD patients and 17 non-depressed AD (nD-AD) patients. R-fMRI datasets were acquired from these D-AD and nD-AD patients. First, we performed a DC analysis to identify voxels that showed altered whole brain functional connectivity (FC) with other voxels. We then further investigated FC using the abnormal DC regions to examine in more detail the connectivity patterns of the identified DC changes. D-AD patients had lower DC values in the right middle frontal, precentral, and postcentral gyrus than nD-AD patients. Seed-based analysis revealed decreased connectivity between the precentral and postcentral gyrus to the supplementary motor area and middle cingulum. FC also decreased in the right middle frontal, precentral, and postcentral gyrus. Thus, AD patients with depression fit a 'network dysfunction model' distinct from major depressive disorder and AD. Copyright © 2016. Published by Elsevier Inc.

A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort.

PubMed

Pedrini, Steve; Gupta, Veer B; Hone, Eugene; Doecke, James; O'Bryant, Sid; James, Ian; Bush, Ashley I; Rowe, Christopher C; Villemagne, Victor L; Ames, David; Masters, Colin L; Martins, Ralph N

2017-10-25

Alzheimer's Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer's participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ε4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ε4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial.

Machine Learning-based Individual Assessment of Cortical Atrophy Pattern in Alzheimer's Disease Spectrum: Development of the Classifier and Longitudinal Evaluation.

PubMed

Lee, Jin San; Kim, Changsoo; Shin, Jeong-Hyeon; Cho, Hanna; Shin, Dae-Seock; Kim, Nakyoung; Kim, Hee Jin; Kim, Yeshin; Lockhart, Samuel N; Na, Duk L; Seo, Sang Won; Seong, Joon-Kyung

2018-03-07

To develop a new method for measuring Alzheimer's disease (AD)-specific similarity of cortical atrophy patterns at the individual-level, we employed an individual-level machine learning algorithm. A total of 869 cognitively normal (CN) individuals and 473 patients with probable AD dementia who underwent high-resolution 3T brain MRI were included. We propose a machine learning-based method for measuring the similarity of an individual subject's cortical atrophy pattern with that of a representative AD patient cohort. In addition, we validated this similarity measure in two longitudinal cohorts consisting of 79 patients with amnestic-mild cognitive impairment (aMCI) and 27 patients with probable AD dementia. Surface-based morphometry classifier for discriminating AD from CN showed sensitivity and specificity values of 87.1% and 93.3%, respectively. In the longitudinal validation study, aMCI-converts had higher atrophy similarity at both baseline (p < 0.001) and first year visits (p < 0.001) relative to non-converters. Similarly, AD patients with faster decline had higher atrophy similarity than slower decliners at baseline (p = 0.042), first year (p = 0.028), and third year visits (p = 0.027). The AD-specific atrophy similarity measure is a novel approach for the prediction of dementia risk and for the evaluation of AD trajectories on an individual subject level.

Evaluating Teachers: The Important Role of Value-Added

ERIC Educational Resources Information Center

Glazerman, Steven; Loeb, Susanna; Goldhaber, Dan; Staiger, Douglas; Raudenbush, Stephen; Whitehurst, Grover

2010-01-01

The evaluation of teachers based on the contribution they make to the learning of their students, "value-added", is an increasingly popular but controversial education reform policy. In this report, the authors highlight and try to clarify four areas of confusion about value-added. The first is between value-added information and the…

Elementary School Students with AD/HD: Predictors of Academic Achievement

ERIC Educational Resources Information Center

DuPaul, G.J.; Volpe, R. J.; Jitendra, A. K.; Lutz, J. G.; Lorah, K. S.; Gruber, R.

2004-01-01

Academic underachievement frequently is associated with attention-deficit/hyperactivity disorder (AD/HD); however, the role of variables beyond AD/HD symptoms and cognitive mediators is unknown. Further, whether prediction models vary (a) relative to non-AD/HD students, (b) between math and reading, and (c) based on how achievement is defined has…

Project Facilitate: An Inservice Education Program for Educators and Parents.

ERIC Educational Resources Information Center

Worthington, Lou Anne; Wortham, Joycelyn Foy; Smith, Cynthia Ruth Blocker; Patterson, David

1997-01-01

Describes "Project Facilitate," an inservice education program that provides educators and parents with a comprehensive overview of attention deficit hyperactivity disorder (AD/HD). The program involves the use of four self-instructional content manuals: AD/HD general knowledge base, legal issues and AD/HD, assessment of children with AD/HD, and…

Review of Systemic Treatment Options for Adult Atopic Dermatitis.

PubMed

Gooderham, Melinda; Lynde, Charles W; Papp, Kim; Bourcier, Marc; Guenther, Lyn; Gulliver, Wayne; Hong, Chih-Ho; Poulin, Yves; Sussman, Gordon; Vender, Ronald

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease resulting from defects in skin barrier and aberrant immune responses. AD significantly affects the quality of life. Not all patients respond to topical therapies, and often systemic therapy is required to control the disease. To review the treatment options for adult AD patients including those options for patients who do not respond adequately or have contraindications to oral systemic therapy. A working group of clinicians with experience managing AD was convened to review the current literature on treatment options for adult AD patients. This review is based on the best available evidence from a published systematic review and an additional literature search. Current treatments for AD are reviewed, including options for adult AD patients who do not respond or have contraindications to current systemic therapies. A new approach with targeted therapies is reviewed based on best available evidence. Many AD patients respond satisfactorily to topical or systemic treatments, but for those patients who do not respond or have contraindications, new biologic agents appear to be promising therapies.

Magnetic resonance imaging based clinical research in Alzheimer's disease.

PubMed

Fayed, Nicolás; Modrego, Pedro J; Salinas, Gulillermo Rojas; Gazulla, José

2012-01-01

Alzheimer's disease (AD) is the most common cause of dementia in elderly people in western countries. However important goals are unmet in the issue of early diagnosis and the development of new drugs for treatment. Magnetic resonance imaging (MRI) and volumetry of the medial temporal lobe structures are useful tools for diagnosis. Positron emission tomography is one of the most sensitive tests for making an early diagnosis of AD but the cost and limited availability are important caveats for its utilization. The importance of magnetic resonance techniques has increased gradually to the extent that most clinical works based on AD use these techniques as the main aid to diagnosis. However, the accuracy of structural MRI as biomarker of early AD generally reaches an accuracy of 80%, so additional biomarkers should be used to improve predictions. Other structural MRI (diffusion weighted, diffusion-tensor MRI) and functional MRI have also added interesting contribution to the understanding of the pathophysiology of AD. Magnetic resonance spectroscopy has proven useful to monitor progression and response to treatment in AD, as well as a biomarker of early AD in mild cognitive impairment.

The Adenovirus Genome Contributes to the Structural Stability of the Virion

PubMed Central

Saha, Bratati; Wong, Carmen M.; Parks, Robin J.

2014-01-01

Adenovirus (Ad) vectors are currently the most commonly used platform for therapeutic gene delivery in human gene therapy clinical trials. Although these vectors are effective, many researchers seek to further improve the safety and efficacy of Ad-based vectors through detailed characterization of basic Ad biology relevant to its function as a vector system. Most Ad vectors are deleted of key, or all, viral protein coding sequences, which functions to not only prevent virus replication but also increase the cloning capacity of the vector for foreign DNA. However, radical modifications to the genome size significantly decreases virion stability, suggesting that the virus genome plays a role in maintaining the physical stability of the Ad virion. Indeed, a similar relationship between genome size and virion stability has been noted for many viruses. This review discusses the impact of the genome size on Ad virion stability and emphasizes the need to consider this aspect of virus biology in Ad-based vector design. PMID:25254384

Anti-Cocaine Vaccine Based on Coupling a Cocaine Analog to a Disrupted Adenovirus

PubMed Central

Koob, George; Hicks, Martin J.; Wee, Sunmee; Rosenberg, Jonathan B.; De, Bishnu P.; Kaminksy, Stephen M.; Moreno, Amira; Janda, Kim D.; Crystal, Ronald G.

2012-01-01

The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. Based on these concepts, we developed dAd5GNE, a disrupted E1−E3− serotype 5 Ad with GNE, a stable cocaine analog, covalently linked to the Ad capsid proteins. In pre-clinical studies, dAd5GNE evoked persistent, high titer, high affinity IgG anti-cocaine antibodies, and was highly effective in blocking cocaine-induced hyperactivity and cocaine self-administration behavior in rats. Future studies will be designed to expand the efficacy studies, carry out relevant toxicology studies, and test dAd5GNE in human cocaine addicts. PMID:22229312

Nanotechnology Based Theranostic Approaches in Alzheimer's Disease Management: Current Status and Future Perspective.

PubMed

Ahmad, Javed; Akhter, Sohail; Rizwanullah, Md; Khan, Mohammad Ahmed; Pigeon, Lucie; Addo, Richard T; Greig, Nigel H; Midoux, Patrick; Pichon, Chantal; Kamal, Mohammad Amjad

2017-01-01

Alzheimer's disease (AD), a cognitive dysfunction/dementia state amongst the elders is characterized by irreversible neurodegeneration due to varied pathophysiology. Up till now, anti-AD drugs having different pharmacology have been developed and used in clinic. Yet, these medications are not curative and only lowering the AD associated symptoms. Improvement in treatment outcome required drug targeting across the blood-brain barrier (BBB) to the central nervous system (CNS) in optimal therapeutic concentration. Nanotechnology based diagnostic tools, drug carriers and theranostics offer highly sensitive molecular detection, effective drug targeting and their combination. Over the past decade, significant works have been done in this area and we have seen very remarkable outocome in AD therapy. Various nanoparticles from organic and inorganic nanomaterial category have successfully been investigated against AD. This paper discussed the role of nanoparticles in early detection of AD, effective drug targeting to brain and theranostic (diagnosis and therapy) approaches in AD's management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Partial E3 Deletion in Replication-Defective Adenoviral Vectors Allows for Stable Expression of Potentially Toxic Transgene Products.

PubMed

Haut, Larissa H; Gill, Amanda L; Kurupati, Raj K; Bian, Ang; Li, Yan; Giles-Davis, Wynetta; Xiang, Zhiquan; Zhou, Xiang Yang; Ertl, Hildegund C J

2016-10-01

Adenovirus (Ad) is used extensively for construction of viral vectors, most commonly with deletion in its E1 and/or E3 genomic regions. Previously, our attempts to insert envelope proteins (Env) of HIV-1 into such vectors based on chimpanzee-derived Ad (AdC) viruses were thwarted. Here, we describe that genetic instability of an E1- and E3-deleted AdC vector of serotype C6 expressing Env of HIV-1 can be overcome by reinsertion of E3 sequences with anti-apoptotic activities. This partial E3 deletion presumably delays premature death of HEK-293 packaging cell lines due to Env-induced cell apoptosis. The same partial E3 deletion also allows for the generation of stable glycoprotein 140 (gp140)- and gp160-expressing Ad vectors based on AdC7, a distinct AdC serotype. Env-expressing AdC vectors containing the partial E3 deletion are genetically stable upon serial cell culture passaging, produce yields comparable to those of other AdC vectors, and induce transgene product-specific antibody responses in mice. A partial E3 deletion thereby allows expansion of the repertoire of transgenes that can be expressed by Ad vectors.

Defining intrinsic vs. extrinsic atopic dermatitis.

PubMed

Karimkhani, Chante; Silverberg, Jonathan I; Dellavalle, Robert P

2015-06-16

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by eczematous lesions, i.e. ill-demarcated erythematous patches and plaques. AD is commonly associated with elevated immunoglobulin E (IgE) and atopic disorders, such as asthma, hay fever, and food allergies. Rackemann and Mallory were some of the first to distinguish between asthma based on the presence ("extrinsic") or absence ("intrinsic") of allergy. This distinction has subsequently been applied to AD based on the presence ("extrinsic") or absence ("intrinsic") of increased IgE and atopic disease. Although the distinction between intrinsic and extrinsic AD is widely used, it remains controversial.

Online Learning for Classification of Alzheimer Disease based on Cortical Thickness and Hippocampal Shape Analysis.

PubMed

Lee, Ga-Young; Kim, Jeonghun; Kim, Ju Han; Kim, Kiwoong; Seong, Joon-Kyung

2014-01-01

Mobile healthcare applications are becoming a growing trend. Also, the prevalence of dementia in modern society is showing a steady growing trend. Among degenerative brain diseases that cause dementia, Alzheimer disease (AD) is the most common. The purpose of this study was to identify AD patients using magnetic resonance imaging in the mobile environment. We propose an incremental classification for mobile healthcare systems. Our classification method is based on incremental learning for AD diagnosis and AD prediction using the cortical thickness data and hippocampus shape. We constructed a classifier based on principal component analysis and linear discriminant analysis. We performed initial learning and mobile subject classification. Initial learning is the group learning part in our server. Our smartphone agent implements the mobile classification and shows various results. With use of cortical thickness data analysis alone, the discrimination accuracy was 87.33% (sensitivity 96.49% and specificity 64.33%). When cortical thickness data and hippocampal shape were analyzed together, the achieved accuracy was 87.52% (sensitivity 96.79% and specificity 63.24%). In this paper, we presented a classification method based on online learning for AD diagnosis by employing both cortical thickness data and hippocampal shape analysis data. Our method was implemented on smartphone devices and discriminated AD patients for normal group.

IMS Version 3 Student Data Base Maintenance Program.

ERIC Educational Resources Information Center

Brown, John R.

Computer routines that update the Instructional Management System (IMS) Version 3 student data base which supports the Southwest Regional Laboratory's (SWRL) student monitoring system are described. Written in IBM System 360 FORTRAN IV, the program updates the data base by adding, changing and deleting records, as well as adding and deleting…

Postmenopausal hormone therapy and Alzheimer disease

PubMed Central

Tuppurainen, Marjo; Rikkonen, Toni; Kivipelto, Miia; Soininen, Hilkka; Kröger, Heikki; Tolppanen, Anna-Maija

2017-01-01

Objective: To explore the association between postmenopausal hormone therapy (HT) and Alzheimer disease (AD). Methods: Twenty-year follow-up data from the Kuopio Osteoporosis Risk Factor and Prevention study cohort were used. Self-administered questionnaires were sent to all women aged 47–56 years, residing in Kuopio Province starting in 1989 until 2009, every 5th year. Register-based information on HT prescriptions was available since 1995. Probable AD cases, based on DSM-IV and National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria, were identified from the special reimbursement register (1999–2009). The study population included 8,195 women (227 cases of incident AD). Results: Postmenopausal estrogen use was not associated with AD risk in register-based or self-reported data (hazard ratio/95% confidence interval 0.92/0.68–1.2, 0.99/0.75–1.3, respectively). Long-term self-reported postmenopausal HT was associated with reduced AD risk (0.53/0.31–0.91). Similar results were obtained with any dementia diagnosis in the hospital discharge register as an outcome. Conclusions: Our results do not provide strong evidence for a protective association between postmenopausal HT use and AD or dementia, although we observed a reduced AD risk among those with long-term self-reported HT use. PMID:28202700

Apathy and emotion-based decision-making in amnesic mild cognitive impairment and Alzheimer's disease.

PubMed

Bayard, Sophie; Jacus, Jean-Pierre; Raffard, Stéphane; Gely-Nargeot, Marie-Christine

2014-01-01

Apathy and reduced emotion-based decision-making are two behavioral modifications independently described in Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). The aims of this study were to investigate decision-making based on emotional feedback processing in AD and aMCI and to study the impact of reduced decision-making performances on apathy. We recruited 20 patients with AD, 20 participants with aMCI, and 20 healthy controls. All participants completed the Lille apathy rating scale (LARS) and the Iowa gambling task (IGT). Both aMCI and AD participants had reduced performances on the IGT and were more apathetic compared to controls without any difference between aMCI and AD groups. For the entire sample, LARS initiation dimension was related to IGT disadvantageous decision-making profile. We provide the first study showing that both aMCI and AD individuals make less profitable decisions than controls, whereas aMCI and AD did not differ. Disadvantageous decision-making profile on the IGT was associated with higher level of apathy on the action initiation dimension. The role of an abnormal IGT performance as a risk factor for the development of apathy needs to be investigated in other clinical populations and in normal aging.

Alzheimer's disease can spare local metacognition despite global anosognosia: revisiting the confidence-accuracy relationship in episodic memory.

PubMed

Gallo, David A; Cramer, Stefanie J; Wong, Jessica T; Bennett, David A

2012-07-01

Alzheimer's disease (AD) can impair metacognition in addition to more basic cognitive functions like memory. However, while global metacognitive inaccuracies are well documented (i.e., low deficit awareness, or anosognosia), the evidence is mixed regarding the effects of AD on local or task-based metacognitive judgments. Here we investigated local metacognition with respect to the confidence-accuracy relationship in episodic memory (i.e., metamemory). AD and control participants studied pictures of common objects and their verbal labels, and then took forced-choice picture recollection tests using the verbal labels as retrieval cues. We found that item-based confidence judgments discriminated between accurate and inaccurate recollection responses in both groups, implicating relatively spared metamemory in AD. By contrast, there was evidence for global metacognitive deficiencies, as AD participants underestimated the severity of their everyday problems compared to an informant's assessment. Within the AD group, individual differences in global metacognition were related to recollection accuracy, and global metacognition for everyday memory problems was related to task-based metacognitive accuracy. These findings suggest that AD can spare the confidence-accuracy relationship in recollection tasks, and that global and local metacognition measures tap overlapping neuropsychological processes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Aircraft monitoring by the fusion of satellite and ground ADS-B data

NASA Astrophysics Data System (ADS)

Zhang, Xuan; Zhang, Jingjing; Wu, Shufan; Cheng, Qian; Zhu, Rui

2018-02-01

The Automatic Dependent Surveillance- Broadcast (ADS-B) system is today a standard equipment on civil aircraft, transmitting periodically data packages containing information of key data such as aircraft ID, position, altitude and intention. It is designed for terrestrial based ground station to monitor air traffic flow in certain regions. Space based ADS-B is the idea to place sensitive receivers on board satellites in orbit, which can receive ADS-B packages and relay them the relevant ground stations. The terrestrial ADS-B receiver has been widely applied for airport information system, help monitor and control traffic flow, etc. However, its coverage is strongly limited by sea or mountain conditions. This paper first introduces the CubeSat mission, then discusses the integrated application of ADS-B data received from ground stations and from satellites, analyze their characteristics with statistical results of comparison, and explore the technologies to fuse these two different data resources for an integrated application. The satellite data is based on a Chinese CubeSat, STU-2C, being launched into space on Sept 25th 2015. The ADS-B data received from two different resources have shown a good complementary each other, such as to increase the coverage of space for air traffic, and to monitor the whole space in a better and complete way.

Application of moisturizer to neonates prevents development of atopic dermatitis.

PubMed

Horimukai, Kenta; Morita, Kumiko; Narita, Masami; Kondo, Mai; Kitazawa, Hiroshi; Nozaki, Makoto; Shigematsu, Yukiko; Yoshida, Kazue; Niizeki, Hironori; Motomura, Ken-Ichiro; Sago, Haruhiko; Takimoto, Tetsuya; Inoue, Eisuke; Kamemura, Norio; Kido, Hiroshi; Hisatsune, Junzo; Sugai, Motoyuki; Murota, Hiroyuki; Katayama, Ichiro; Sasaki, Takashi; Amagai, Masayuki; Morita, Hideaki; Matsuda, Akio; Matsumoto, Kenji; Saito, Hirohisa; Ohya, Yukihiro

2014-10-01

Recent studies have suggested that epidermal barrier dysfunction contributes to the development of atopic dermatitis (AD) and other allergic diseases. We performed a prospective, randomized controlled trial to investigate whether protecting the skin barrier with a moisturizer during the neonatal period prevents development of AD and allergic sensitization. An emulsion-type moisturizer was applied daily during the first 32 weeks of life to 59 of 118 neonates at high risk for AD (based on having a parent or sibling with AD) who were enrolled in this study. The onset of AD (eczematous symptoms lasting >4 weeks) and eczema (lasting >2 weeks) was assessed by a dermatology specialist on the basis of the modified Hanifin and Rajka criteria. The primary outcome was the cumulative incidence of AD plus eczema (AD/eczema) at week 32 of life. A secondary outcome, allergic sensitization, was evaluated based on serum levels of allergen-specific IgE determined by using a high-sensitivity allergen microarray of diamond-like carbon-coated chips. Approximately 32% fewer neonates who received the moisturizer had AD/eczema by week 32 than control subjects (P = .012, log-rank test). We did not show a statistically significant effect of emollient on allergic sensitization based on the level of IgE antibody against egg white at 0.34 kUA/L CAP-FEIA equivalents. However, the sensitization rate was significantly higher in infants who had AD/eczema than in those who did not (odds ratio, 2.86; 95% CI, 1.22-6.73). Daily application of moisturizer during the first 32 weeks of life reduces the risk of AD/eczema in infants. Allergic sensitization during this time period is associated with the presence of eczematous skin but not with moisturizer use. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Toward systems neuroscience in mild cognitive impairment and Alzheimer's disease: a meta-analysis of 75 fMRI studies.

PubMed

Li, Hui-Jie; Hou, Xiao-Hui; Liu, Han-Hui; Yue, Chun-Lin; He, Yong; Zuo, Xi-Nian

2015-03-01

Most of the previous task functional magnetic resonance imaging (fMRI) studies found abnormalities in distributed brain regions in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and few studies investigated the brain network dysfunction from the system level. In this meta-analysis, we aimed to examine brain network dysfunction in MCI and AD. We systematically searched task-based fMRI studies in MCI and AD published between January 1990 and January 2014. Activation likelihood estimation meta-analyses were conducted to compare the significant group differences in brain activation, the significant voxels were overlaid onto seven referenced neuronal cortical networks derived from the resting-state fMRI data of 1,000 healthy participants. Thirty-nine task-based fMRI studies (697 MCI patients and 628 healthy controls) were included in MCI-related meta-analysis while 36 task-based fMRI studies (421 AD patients and 512 healthy controls) were included in AD-related meta-analysis. The meta-analytic results revealed that MCI and AD showed abnormal regional brain activation as well as large-scale brain networks. MCI patients showed hypoactivation in default, frontoparietal, and visual networks relative to healthy controls, whereas AD-related hypoactivation mainly located in visual, default, and ventral attention networks relative to healthy controls. Both MCI-related and AD-related hyperactivation fell in frontoparietal, ventral attention, default, and somatomotor networks relative to healthy controls. MCI and AD presented different pathological while shared similar compensatory large-scale networks in fulfilling the cognitive tasks. These system-level findings are helpful to link the fundamental declines of cognitive tasks to brain networks in MCI and AD. © 2014 Wiley Periodicals, Inc.

Interfacial molecular interactions based on the conformation recognition between the insoluble antitumor drug AD-1 and DSPC.

PubMed

Yin, Tian; Cao, Xiuxiu; Liu, Xiaolin; Wang, Jian; Shi, Caihong; Su, Jia; Zhang, Yu; Gou, Jingxin; He, Haibing; Guo, Haiyan; Tang, Xing; Zhao, Yuqing

2016-10-01

In this study, molecular interactions between the anti-cancer agent 20(R)-25-methoxyl-dammarane-3β, 12β, 20-triol (AD-1) and phospholipid 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) were investigated using the Langmuir film balance technique. The characteristics of binary Langmuir monolayers consisting of DSPC and AD-1 were conducted on the basis of the surface pressure-area per molecule (π-A) isotherms. It was found that the drug was able to become efficiently inserted into preformed DSPC monolayers, indicating a preferential interaction between AD-1 and DSPC. For the examined lateral pressure at 20mN/m, the largest negative values of ΔGex were found for the AD-1/DSPC monolayer, which should be the most stable. Based on the calculated values of ΔGex, we found that the AD-1/DSPC systems exhibited the best mixed characteristics when the molar fraction of the AD-1 was 0.8; at that relative concentration, the AD-1 molecules can mix better and interact with the phospholipid molecules. In addition, the drug-DSPC binary supramolecular structure was also deposited on the mica plates as shown by atomic force microscopy (AFM). Finally, molecular docking calculations explained satisfactorily that, based on the conformations interactions (conformation recognition), even at an AD-1/DSPC molar ratio as high as 8:2, the interfacial stabilization of the AD-1/DSPC system was fairly strong due to hydrophobic interactions. A higher loading capacity of DSPC might be possible, as it is associated with a more flexible geometrical environment, which allows these supramolecular structures to accept larger increases in drug loading upon steric binding. Copyright © 2016 Elsevier B.V. All rights reserved.

Multicasting in Wireless Communications (Ad-Hoc Networks): Comparison against a Tree-Based Approach

NASA Astrophysics Data System (ADS)

Rizos, G. E.; Vasiliadis, D. C.

2007-12-01

We examine on-demand multicasting in ad hoc networks. The Core Assisted Mesh Protocol (CAMP) is a well-known protocol for multicast routing in ad-hoc networks, generalizing the notion of core-based trees employed for internet multicasting into multicast meshes that have much richer connectivity than trees. On the other hand, wireless tree-based multicast routing protocols use much simpler structures for determining route paths, using only parent-child relationships. In this work, we compare the performance of the CAMP protocol against the performance of wireless tree-based multicast routing protocols, in terms of two important factors, namely packet delay and ratio of dropped packets.

Design and synthesis of novel adenine fluorescence probe based on Eu(III) complexes with dtpa-bis(guanine) ligand

NASA Astrophysics Data System (ADS)

Tian, Fengyun; Jiang, Xiaoqing; Dou, Xuekai; Wu, Qiong; Wang, Jun; Song, Youtao

2017-05-01

A novel adenine (Ad) fluorescence probe (EuIII-dtpa-bis(guanine)) was designed and synthesized by improving experimental method based on the Eu(III) complex and dtpa-bis(guanine) ligand. The dtpa-bis(guanine) ligand was first synthesized by the acylation action between dtpaa and guanine (Gu), and the corresponding Eu(III) complex was successfully prepared through heat-refluxing method with dtpa-bis(guanine) ligand. As a novel fluorescence probe, the EuIII-dtpa-bis(guanine) complex can detect adenine (Ad) with characteristics of strong targeting, high specificity and high recognition ability. The detection mechanism of the adenine (Ad) using this probe in buffer solution was studied by ultraviolet-visible (UV-vis) and fluorescence spectroscopy. When the EuIII-dtpa-bis(guanine) was introduced to the adenine (Ad) solution, the fluorescence emission intensity was significantly enhanced. However, adding other bases such as guanine (Gu), xanthine (Xa), hypoxanthine (Hy) and uric acid (Ur) with similar composition and structure to that of adenine (Ad) to the EuIII-dtpa-bis(guanine) solution, the fluorescence emission intensities are nearly invariable. Meanwhile, the interference of guanine (Gu), xanthine (Xa), hypoxanthine (Hy) and uric acid (Ur) on the detection of the adenine using EuIII-dtpa-bis(guanine) probe was also studied. It was found that presence of these bases does not affect the detection of adenine (Ad). A linear response of fluorescence emission intensities of EuIII-dtpa-bis(guanine) at 570 nm as a function of adenine (Ad) concentration in the range of 0.00-5.00 × 10- 5 mol L- 1 was observed. The detection limit is about 4.70 × 10- 7 mol L- 1.

Consensus Guidelines for the Treatment of Atopic Dermatitis in Korea (Part I): General Management and Topical Treatment

PubMed Central

Kim, Jung Eun; Kim, Hyun Jeong; Lew, Bark-Lynn; Lee, Kyung Ho; Hong, Seung Phil; Jang, Yong Hyun; Park, Kui Young; Seo, Seong Jun; Bae, Jung Min; Choi, Eung Ho; Suhr, Ki Beom; Lee, Seung Chul; Ko, Hyun Chang; Park, Young Lip; Son, Sang Wook; Seo, Young Jun; Lee, Yang Won; Cho, Sang Hyun; Park, Chun Wook

2015-01-01

Background Since the treatment guidelines for atopic dermatitis (AD) were released by the Korean Atopic Dermatitis Association (KADA) work group in 2006, there have been several advances in AD management. Objective We aimed to establish updated evidence- and experience-based treatment guidelines for Korean AD. Methods We collected a database of references from relevant systematic AD reviews and guidelines regarding general AD management such as bathing and skin care, avoidance of exacerbating factors, education and psychosocial support, and the use of moisturizers and topical anti-inflammatory and antipruritic drugs. Evidence for each statement was graded and the strength of the recommendation for each statement classified. Thirty-nine KADA council members participated in three rounds of voting to establish an expert consensus of recommendations. Results Basic AD treatment includes proper bathing and skin care, avoidance of exacerbating factors, proper education and psychosocial support, and use of moisturizers. The regular use of moisturizer has a steroid-sparing effect and reduces relapse episodes. The short- and long-term use of topical corticosteroids and calcineurin inhibitors improves AD symptoms and should be encouraged to use in an active and proactive treatment. Wet-wrap therapy can be used for rapid recovery of acute exacerbation. Topical antipruritic drugs cannot be recommended for the treatment of AD. Conclusion This report provides up-to-date evidence- and experience-based treatment guidelines for AD regarding general management and topical treatment. In addition, the average agreement scores obtained by a panel of experts based on the Korean healthcare system and patient adherence are presented. PMID:26512171

Species B adenovirus serotypes 3, 7, 11 and 35 share similar binding sites on the membrane cofactor protein CD46 receptor.

PubMed

Fleischli, Christoph; Sirena, Dominique; Lesage, Guillaume; Havenga, Menzo J E; Cattaneo, Roberto; Greber, Urs F; Hemmi, Silvio

2007-11-01

We recently characterized the domains of the human cofactor protein CD46 involved in binding species B2 adenovirus (Ad) serotype 35. Here, the CD46 binding determinants are mapped for the species B1 Ad serotypes 3 and 7 and for the species B2 Ad11. Ad3, 7 and 11 bound and transduced CD46-positive rodent BHK cells at levels similar to Ad35. By using antibody-blocking experiments, hybrid CD46-CD4 receptor constructs and CD46 single point mutants, it is shown that Ad3, 7 and 11 share many of the Ad35-binding features on CD46. Both CD46 short consensus repeat domains SCR I and SCR II were necessary and sufficient for optimal binding and transgene expression, provided that they were positioned at an appropriate distance from the cell membrane. Similar to Ad35, most of the putative binding residues of Ad3, 7 and 11 were located on the same glycan-free, solvent-exposed face of the SCR I or SCR II domains, largely overlapping with the binding surface of the recently solved fiber knob Ad11-SCR I-II three-dimensional structure. Differences between species B1 and B2 Ads were documented with competition experiments based on anti-CD46 antibodies directed against epitopes flanking the putative Ad-binding sites, and with competition experiments based on soluble CD46 protein. It is concluded that the B1 and B2 species of Ad engage CD46 through similar binding surfaces.

White Matter Hyperintensities and Changes in White Matter Integrity in Patients with Alzheimer’s Disease

PubMed Central

Wang, Liya; Goldstein, Felicia C.; Levey, Allan I.; Lah, James J.; Meltzer, Carolyn C.; Holder, Chad A.; Mao, Hui

2012-01-01

Purpose White matter hyperintensities (WMHs) are a risk factor for Alzheimer’s disease (AD). This study investigated the relationship between WMHs and white matter changes in AD using diffusion tensor imaging (DTI) and the sensitivity of each DTI index in distinguishing AD with WMHs. Subjects and Methods Forty-four subjects with WMHs were included. Subjects were classified into three groups based on the Scheltens rating scale: 15 AD patients with mild WMHs, 12 AD patients with severe WMHs, and 17 controls with mild WMHs. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (DR) and axial diffusivity (DA) were analyzed using the region of interest and Tract-Based Spatial Statistics methods. Sensitivity and specificity of DTI indices in distinguishing AD groups from the controls were evaluated. Results AD patients with mild WMHs exhibited differences from control subjects in most DTI indices in the medial temporal and frontal areas; however, differences in DTI indices from AD patients with mild WMHs and AD patients with severe WMHs were found in the parietal and occipital areas. FA and DR were more sensitive measurements than MD and DA in differentiating AD patients from controls, while MD was a more sensitive measurement in distinguishing AD patients with severe WMHs from those with mild WMHs. Conclusions WMHs may contribute to the white matter changes in AD brains, specifically in temporal and frontal areas. Changes in parietal and occipital lobes may be related to the severity of WMHs. DR may serve as an imaging marker of myelin deficits associated with AD. PMID:21152911

Identification of Physician-Diagnosed Alzheimer's Disease and Related Dementias in Population-Based Administrative Data: A Validation Study Using Family Physicians' Electronic Medical Records.

PubMed

Jaakkimainen, R Liisa; Bronskill, Susan E; Tierney, Mary C; Herrmann, Nathan; Green, Diane; Young, Jacqueline; Ivers, Noah; Butt, Debra; Widdifield, Jessica; Tu, Karen

2016-08-10

Population-based surveillance of Alzheimer's and related dementias (AD-RD) incidence and prevalence is important for chronic disease management and health system capacity planning. Algorithms based on health administrative data have been successfully developed for many chronic conditions. The increasing use of electronic medical records (EMRs) by family physicians (FPs) provides a novel reference standard by which to evaluate these algorithms as FPs are the first point of contact and providers of ongoing medical care for persons with AD-RD. We used FP EMR data as the reference standard to evaluate the accuracy of population-based health administrative data in identifying older adults with AD-RD over time. This retrospective chart abstraction study used a random sample of EMRs for 3,404 adults over 65 years of age from 83 community-based FPs in Ontario, Canada. AD-RD patients identified in the EMR were used as the reference standard against which algorithms identifying cases of AD-RD in administrative databases were compared. The highest performing algorithm was "one hospitalization code OR (three physician claims codes at least 30 days apart in a two year period) OR a prescription filled for an AD-RD specific medication" with sensitivity 79.3% (confidence interval (CI) 72.9-85.8%), specificity 99.1% (CI 98.8-99.4%), positive predictive value 80.4% (CI 74.0-86.8%), and negative predictive value 99.0% (CI 98.7-99.4%). This resulted in an age- and sex-adjusted incidence of 18.1 per 1,000 persons and adjusted prevalence of 72.0 per 1,000 persons in 2010/11. Algorithms developed from health administrative data are sensitive and specific for identifying older adults with AD-RD.

A systematic analysis of genomic changes in Tg2576 mice.

PubMed

Tan, Lu; Wang, Xiong; Ni, Zhong-Fei; Zhu, Xiuming; Wu, Wei; Zhu, Ling-Qiang; Liu, Dan

2013-06-01

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by intelligence decline, behavioral disorders and cognitive disability. The purpose of this study was to investigate gene expression in AD, based on published microarray data on Tg2576 mice. Hierarchical Cluster Analysis and Gene Ontology were employed to group genes together on the basis of their product characteristics and annotation data. Genes with prominent alterations were clustered into apoptosis and axon guidance pathways. Based on our findings and those of previous studies, we propose that the mitochondria-mediated apoptotic pathway plays a crucial role in the neuronal loss and synaptic dysfunction associated with AD. Furthermore, based on the findings of Positional Gene Enrichment analysis and Gene Set Enrichment analysis, we propose that the regulation of transcription of AD genes may be an important pathogenic factor in this neurodegenerative disease. Our results highlight the importance of genes that could subsequently be examined for their potential as prognostic markers for AD.

Japanese Alzheimer's Disease and Other Complex Disorders Diagnosis Based on Mitochondrial SNP Haplogroups

PubMed Central

Takasaki, Shigeru

2012-01-01

This paper first explains how the relations between Japanese Alzheimer's disease (AD) patients and their mitochondrial SNP frequencies at individual mtDNA positions examined using the radial basis function (RBF) network and a method based on RBF network predictions and that Japanese AD patients are associated with the haplogroups G2a and N9b1. It then describes a method for the initial diagnosis of Alzheimer's disease that is based on the mtSNP haplogroups of the AD patients. The method examines the relations between someone's mtDNA mutations and the mtSNPs of AD patients. As the mtSNP haplogroups thus obtained indicate which nucleotides of mtDNA loci are changed in the Alzheimer's patients, a person's probability of becoming an AD patient can be predicted by comparing those mtDNA mutations with that person's mtDNA mutations. The proposed method can also be used to diagnose diseases such as Parkinson's disease and type 2 diabetes and to identify people likely to become centenarians. PMID:22848858

Spinning AdS loop diagrams: two point functions

NASA Astrophysics Data System (ADS)

Giombi, Simone; Sleight, Charlotte; Taronna, Massimo

2018-06-01

We develop a systematic approach to evaluating AdS loop amplitudes with spinning legs based on the spectral (or "split") representation of bulk-to-bulk propagators, which re-expresses loop diagrams in terms of spectral integrals and higher-point tree diagrams. In this work we focus on 2pt one-loop Witten diagrams involving totally symmetric fields of arbitrary mass and integer spin. As an application of this framework, we study the contribution to the anomalous dimension of higher-spin currents generated by bubble diagrams in higher-spin gauge theories on AdS.

Natural products as a rich source of tau-targeting drugs for Alzheimer’s disease

PubMed Central

Calcul, Laurent; Zhang, Bo; Jinwal, Umesh K; Dickey, Chad A; Baker, Bill J

2013-01-01

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common form of dementia, affecting more than 5.4 million people in the USA. Although the cause of AD is not well understood, the cholinergic, amyloid and tau hypotheses were proposed to explain its development. Drug discovery for AD based on the cholinergic and amyloid theories have not been effective. In this article we summarize tau-based natural products as AD therapeutics from a variety of biological sources, including the anti-amyloid agent curcumin, isolated from turmeric, the microtubule stabilizer paclitaxel, from the Pacific Yew Taxus brevifolia, and the Streptomyces-derived Hsp90 inhibitor, geldanamycin. The overlooked approach of clearing tau aggregation will most likely be the next objective for AD drug discovery. PMID:22924511

Combining anatomical, diffusion, and resting state functional magnetic resonance imaging for individual classification of mild and moderate Alzheimer's disease.

PubMed

Schouten, Tijn M; Koini, Marisa; de Vos, Frank; Seiler, Stephan; van der Grond, Jeroen; Lechner, Anita; Hafkemeijer, Anne; Möller, Christiane; Schmidt, Reinhold; de Rooij, Mark; Rombouts, Serge A R B

2016-01-01

Magnetic resonance imaging (MRI) is sensitive to structural and functional changes in the brain caused by Alzheimer's disease (AD), and can therefore be used to help in diagnosing the disease. Improving classification of AD patients based on MRI scans might help to identify AD earlier in the disease's progress, which may be key in developing treatments for AD. In this study we used an elastic net classifier based on several measures derived from the MRI scans of mild to moderate AD patients (N = 77) from the prospective registry on dementia study and controls (N = 173) from the Austrian Stroke Prevention Family Study. We based our classification on measures from anatomical MRI, diffusion weighted MRI and resting state functional MRI. Our unimodal classification performance ranged from an area under the curve (AUC) of 0.760 (full correlations between functional networks) to 0.909 (grey matter density). When combining measures from multiple modalities in a stepwise manner, the classification performance improved to an AUC of 0.952. This optimal combination consisted of grey matter density, white matter density, fractional anisotropy, mean diffusivity, and sparse partial correlations between functional networks. Classification performance for mild AD as well as moderate AD also improved when using this multimodal combination. We conclude that different MRI modalities provide complementary information for classifying AD. Moreover, combining multiple modalities can substantially improve classification performance over unimodal classification.

A Multilevel Latent Growth Curve Approach to Predicting Student Proficiency

ERIC Educational Resources Information Center

Choi, Kilchan; Goldschmidt, Pete

2012-01-01

Value-added models and growth-based accountability aim to evaluate school's performance based on student growth in learning. The current focus is on linking the results from value-added models to the ones from growth-based accountability systems including Adequate Yearly Progress decisions mandated by No Child Left Behind. We present a new…

37 CFR 2.35 - Adding, deleting, or substituting bases.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Adding, deleting, or substituting bases. 2.35 Section 2.35 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK..., deleting, or substituting bases. (a) In an application under section 66(a) of the Act, an applicant may not...

37 CFR 2.35 - Adding, deleting, or substituting bases.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Adding, deleting, or substituting bases. 2.35 Section 2.35 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK..., deleting, or substituting bases. (a) In an application under section 66(a) of the Act, an applicant may not...

37 CFR 2.35 - Adding, deleting, or substituting bases.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Adding, deleting, or substituting bases. 2.35 Section 2.35 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK..., deleting, or substituting bases. (a) In an application under section 66(a) of the Act, an applicant may not...

37 CFR 2.35 - Adding, deleting, or substituting bases.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Adding, deleting, or substituting bases. 2.35 Section 2.35 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK..., deleting, or substituting bases. (a) In an application under section 66(a) of the Act, an applicant may not...

Ad hoc Laser networks component technology for modular spacecraft

NASA Astrophysics Data System (ADS)

Huang, Xiujun; Shi, Dele; Ma, Zongfeng; Shen, Jingshi

2016-03-01

Distributed reconfigurable satellite is a new kind of spacecraft system, which is based on a flexible platform of modularization and standardization. Based on the module data flow analysis of the spacecraft, this paper proposes a network component of ad hoc Laser networks architecture. Low speed control network with high speed load network of Microwave-Laser communication mode, no mesh network mode, to improve the flexibility of the network. Ad hoc Laser networks component technology was developed, and carried out the related performance testing and experiment. The results showed that ad hoc Laser networks components can meet the demand of future networking between the module of spacecraft.

Ad hoc laser networks component technology for modular spacecraft

NASA Astrophysics Data System (ADS)

Huang, Xiujun; Shi, Dele; Shen, Jingshi

2017-10-01

Distributed reconfigurable satellite is a new kind of spacecraft system, which is based on a flexible platform of modularization and standardization. Based on the module data flow analysis of the spacecraft, this paper proposes a network component of ad hoc Laser networks architecture. Low speed control network with high speed load network of Microwave-Laser communication mode, no mesh network mode, to improve the flexibility of the network. Ad hoc Laser networks component technology was developed, and carried out the related performance testing and experiment. The results showed that ad hoc Laser networks components can meet the demand of future networking between the module of spacecraft.

A serum protein-based algorithm for the detection of Alzheimer disease.

PubMed

O'Bryant, Sid E; Xiao, Guanghua; Barber, Robert; Reisch, Joan; Doody, Rachelle; Fairchild, Thomas; Adams, Perrie; Waring, Steven; Diaz-Arrastia, Ramon

2010-09-01

To develop an algorithm that separates patients with Alzheimer disease (AD) from controls. Longitudinal case-control study. The Texas Alzheimer's Research Consortium project. Patients  We analyzed serum protein-based multiplex biomarker data from 197 patients diagnosed with AD and 203 controls. Main Outcome Measure  The total sample was randomized equally into training and test sets and random forest methods were applied to the training set to create a biomarker risk score. The biomarker risk score had a sensitivity and specificity of 0.80 and 0.91, respectively, and an area under the curve of 0.91 in detecting AD. When age, sex, education, and APOE status were added to the algorithm, the sensitivity, specificity, and area under the curve were 0.94, 0.84, and 0.95, respectively. These initial data suggest that serum protein-based biomarkers can be combined with clinical information to accurately classify AD. A disproportionate number of inflammatory and vascular markers were weighted most heavily in the analyses. Additionally, these markers consistently distinguished cases from controls in significant analysis of microarray, logistic regression, and Wilcoxon analyses, suggesting the existence of an inflammatory-related endophenotype of AD that may provide targeted therapeutic opportunities for this subset of patients.

Alzheimer Disease and Behavioral Variant Frontotemporal Dementia: Automatic Classification Based on Cortical Atrophy for Single-Subject Diagnosis.

PubMed

Möller, Christiane; Pijnenburg, Yolande A L; van der Flier, Wiesje M; Versteeg, Adriaan; Tijms, Betty; de Munck, Jan C; Hafkemeijer, Anne; Rombouts, Serge A R B; van der Grond, Jeroen; van Swieten, John; Dopper, Elise; Scheltens, Philip; Barkhof, Frederik; Vrenken, Hugo; Wink, Alle Meije

2016-06-01

Purpose To investigate the diagnostic accuracy of an image-based classifier to distinguish between Alzheimer disease (AD) and behavioral variant frontotemporal dementia (bvFTD) in individual patients by using gray matter (GM) density maps computed from standard T1-weighted structural images obtained with multiple imagers and with independent training and prediction data. Materials and Methods The local institutional review board approved the study. Eighty-four patients with AD, 51 patients with bvFTD, and 94 control subjects were divided into independent training (n = 115) and prediction (n = 114) sets with identical diagnosis and imager type distributions. Training of a support vector machine (SVM) classifier used diagnostic status and GM density maps and produced voxelwise discrimination maps. Discriminant function analysis was used to estimate suitability of the extracted weights for single-subject classification in the prediction set. Receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were calculated for image-based classifiers and neuropsychological z scores. Results Training accuracy of the SVM was 85% for patients with AD versus control subjects, 72% for patients with bvFTD versus control subjects, and 79% for patients with AD versus patients with bvFTD (P ≤ .029). Single-subject diagnosis in the prediction set when using the discrimination maps yielded accuracies of 88% for patients with AD versus control subjects, 85% for patients with bvFTD versus control subjects, and 82% for patients with AD versus patients with bvFTD, with a good to excellent AUC (range, 0.81-0.95; P ≤ .001). Machine learning-based categorization of AD versus bvFTD based on GM density maps outperforms classification based on neuropsychological test results. Conclusion The SVM can be used in single-subject discrimination and can help the clinician arrive at a diagnosis. The SVM can be used to distinguish disease-specific GM patterns in patients with AD and those with bvFTD as compared with normal aging by using common T1-weighted structural MR imaging. (©) RSNA, 2015.

Drug prescription patterns in patients with Addison's disease: a Swedish population-based cohort study.

PubMed

Björnsdottir, Sigridur; Sundström, Anders; Ludvigsson, Jonas F; Blomqvist, Paul; Kämpe, Olle; Bensing, Sophie

2013-05-01

There are no published data on drug prescription in patients with Addison's disease (AD). Our objective was to describe the drug prescription patterns in Swedish AD patients before and after diagnosis compared with population controls. We conducted a population-based cohort study in Sweden. Through the Swedish National Patient Register and the Swedish Prescribed Drug Register, we identified 1305 patients with both a diagnosis of AD and on combination treatment with hydrocortisone/cortisone acetate and fludrocortisone. Direct evidence of the AD diagnosis from patient charts was not available. We identified 11 996 matched controls by the Register of Population. We determined the ratio of observed to expected number of patients treated with prescribed drugs. Overall, Swedish AD patients received more prescribed drugs than controls, and 59.3% of the AD patients had medications indicating concomitant autoimmune disease. Interestingly, both before and after the diagnosis of AD, patients used more gastrointestinal medications, antianemic preparations, lipid-modifying agents, antibiotics for systemic use, hypnotics and sedatives, and drugs for obstructive airway disease (all P values < .05). Notably, an increased prescription of several antihypertensive drugs and high-ceiling diuretics was observed after the diagnosis of AD. Gastrointestinal symptoms and anemia, especially in conjunction with autoimmune disorders, should alert the physician about the possibility of AD. The higher use of drugs for cardiovascular disorders after diagnosis in patients with AD raises concerns about the replacement therapy.

Localization of neutralization epitopes on adenovirus fiber knob from species C.

PubMed

Lang, Shuai; Wang, Lizheng; Wang, Zixuan; Zhu, Rui; Yan, Jingyi; Wang, Baoming; Wu, Jiaxin; Zhang, Haihong; Wu, Hui; Zhou, Yan; Kong, Wei; Yu, Bin; Yu, Xianghui

2016-04-01

Although potential neutralization epitopes on the fiber knob of adenovirus (AdV) serotype 2 (Ad2) and Ad5 have been revealed, few studies have been carried out to identify neutralization epitopes on the knob from a broader panel of AdV serotypes. In this study, based on sequence and structural analysis of knobs from Ad1, Ad2, Ad5 and Ad6 (all from species C), several trimeric chimeric knob proteins were expressed in Escherichia coli to identify the locations of neutralization epitopes on the knobs by analysing their reactivity with mouse and rabbit polyclonal sera raised against AdVs and human sera with natural AdV infection. The dominant neutralization epitopes were located mainly in the N-terminal part of knobs from Ad1, Ad2 and Ad5, but they seemed to be located in the C-terminal part of the Ad6 knob, with some individual differences in rabbit and human populations. Our study adds to our understanding of humoral immune responses to AdVs and will facilitate the construction of more desirable capsid-modified recombinant Ad5 vectors.

Stem cell-based gene therapy activated using magnetic hyperthermia to enhance the treatment of cancer

PubMed Central

Yin, Perry T.; Shah, Shreyas; Pasquale, Nicholas J.; Garbuzenko, Olga B.; Minko, Tamara; Lee, Ki-Bum

2015-01-01

Stem cell-based gene therapies, wherein stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential for cancer applications owing to their innate ability to home to tumors. However, traditional stem cell-based gene therapies are hampered by our current inability to control when the therapeutic genes are actually turned on, thereby resulting in detrimental side effects. Here, we report the novel application of magnetic core-shell nanoparticles for the dual purpose of delivering and activating a heat-inducible gene vector that encodes TNF-related apoptosis-inducing ligand (TRAIL) in adipose-derived mesenchymal stem cells (AD-MSCs). By combining the tumor tropism of the AD-MSCs with the spatiotemporal MCNP-based delivery and activation of TRAIL expression, this platform provides an attractive means with which to enhance our control over the activation of stem cell-based gene therapies. In particular, we found that these engineered AD-MSCs retained their innate ability to proliferate, differentiate, and, most importantly, home to tumors, making them ideal cellular carriers. Moreover, exposure of the engineered AD-MSCS to mild magnetic hyperthermia resulted in the selective expression of TRAIL from the engineered AD-MSCs and, as a result, induced significant ovarian cancer cell death in vitro and in vivo. PMID:26720500

Stem cell-based gene therapy activated using magnetic hyperthermia to enhance the treatment of cancer.

PubMed

Yin, Perry T; Shah, Shreyas; Pasquale, Nicholas J; Garbuzenko, Olga B; Minko, Tamara; Lee, Ki-Bum

2016-03-01

Stem cell-based gene therapies, wherein stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential for cancer applications owing to their innate ability to home to tumors. However, traditional stem cell-based gene therapies are hampered by our current inability to control when the therapeutic genes are actually turned on, thereby resulting in detrimental side effects. Here, we report the novel application of magnetic core-shell nanoparticles for the dual purpose of delivering and activating a heat-inducible gene vector that encodes TNF-related apoptosis-inducing ligand (TRAIL) in adipose-derived mesenchymal stem cells (AD-MSCs). By combining the tumor tropism of the AD-MSCs with the spatiotemporal MCNP-based delivery and activation of TRAIL expression, this platform provides an attractive means with which to enhance our control over the activation of stem cell-based gene therapies. In particular, we found that these engineered AD-MSCs retained their innate ability to proliferate, differentiate, and, most importantly, home to tumors, making them ideal cellular carriers. Moreover, exposure of the engineered AD-MSCS to mild magnetic hyperthermia resulted in the selective expression of TRAIL from the engineered AD-MSCs and, as a result, induced significant ovarian cancer cell death in vitro and in vivo. Copyright © 2015 Elsevier Ltd. All rights reserved.

Study of activity based costing implementation for palm oil production using value-added and non-value-added activity consideration in PT XYZ palm oil mill

NASA Astrophysics Data System (ADS)

Sembiring, M. T.; Wahyuni, D.; Sinaga, T. S.; Silaban, A.

2018-02-01

Cost allocation at manufacturing industry particularly in Palm Oil Mill still widely practiced based on estimation. It leads to cost distortion. Besides, processing time determined by company is not in accordance with actual processing time in work station. Hence, the purpose of this study is to eliminates non-value-added activities therefore processing time could be shortened and production cost could be reduced. Activity Based Costing Method is used in this research to calculate production cost with Value Added and Non-Value-Added Activities consideration. The result of this study is processing time decreasing for 35.75% at Weighting Bridge Station, 29.77% at Sorting Station, 5.05% at Loading Ramp Station, and 0.79% at Sterilizer Station. Cost of Manufactured for Crude Palm Oil are IDR 5.236,81/kg calculated by Traditional Method, IDR 4.583,37/kg calculated by Activity Based Costing Method before implementation of Activity Improvement and IDR 4.581,71/kg after implementation of Activity Improvement Meanwhile Cost of Manufactured for Palm Kernel are IDR 2.159,50/kg calculated by Traditional Method, IDR 4.584,63/kg calculated by Activity Based Costing Method before implementation of Activity Improvement and IDR 4.582,97/kg after implementation of Activity Improvement.

Production of adenovirus vectors and their use as a delivery system for influenza vaccines

PubMed Central

Vemula, Sai V.; Mittal, Suresh K.

2010-01-01

IMPORTANCE OF THE FIELD With the emergence of highly pathogenic avian influenza H5N1 viruses that have crossed species barriers and are responsible for lethal infections in humans in many countries, there is an urgent need for the development of effective vaccines which can be produced in large quantities at a short notice and confer broad protection against these H5N1 variants. In order to meet the potential global vaccine demand in a pandemic scenario, new vaccine-production strategies must be explored in addition to the currently used egg-based technology for seasonal influenza. AREAS COVERED IN THIS REVIEW Adenovirus (Ad) based influenza vaccines represent an attractive alternative/supplement to the currently licensed egg-based influenza vaccines. Ad-based vaccines are relatively inexpensive to manufacture, and their production process does not require either chicken eggs or labor intensive and time-consuming processes necessitating enhanced biosafety facilities. Most importantly, in a pandemic situation, this vaccine strategy could offer a stockpiling option to reduce the response time before a strain-matched vaccine could be developed. WHAT THE READER WILL GAIN This review discusses Ad-vector technology and the current progress in the development of Ad-based influenza vaccines. TAKE HOME MESSAGE Ad vector-based influenza vaccines for pandemic preparedness are under development to meet the global vaccine demand. PMID:20822477

Fully automated atlas-based hippocampal volumetry for detection of Alzheimer's disease in a memory clinic setting.

PubMed

Suppa, Per; Anker, Ulrich; Spies, Lothar; Bopp, Irene; Rüegger-Frey, Brigitte; Klaghofer, Richard; Gocke, Carola; Hampel, Harald; Beck, Sacha; Buchert, Ralph

2015-01-01

Hippocampal volume is a promising biomarker to enhance the accuracy of the diagnosis of dementia due to Alzheimer's disease (AD). However, whereas hippocampal volume is well studied in patient samples from clinical trials, its value in clinical routine patient care is still rather unclear. The aim of the present study, therefore, was to evaluate fully automated atlas-based hippocampal volumetry for detection of AD in the setting of a secondary care expert memory clinic for outpatients. One-hundred consecutive patients with memory complaints were clinically evaluated and categorized into three diagnostic groups: AD, intermediate AD, and non-AD. A software tool based on open source software (Statistical Parametric Mapping SPM8) was employed for fully automated tissue segmentation and stereotactical normalization of high-resolution three-dimensional T1-weighted magnetic resonance images. Predefined standard masks were used for computation of grey matter volume of the left and right hippocampus which then was scaled to the patient's total grey matter volume. The right hippocampal volume provided an area under the receiver operating characteristic curve of 84% for detection of AD patients in the whole sample. This indicates that fully automated MR-based hippocampal volumetry fulfills the requirements for a relevant core feasible biomarker for detection of AD in everyday patient care in a secondary care memory clinic for outpatients. The software used in the present study has been made freely available as an SPM8 toolbox. It is robust and fast so that it is easily integrated into routine workflow.

Biomarkers in Sporadic and Familial Alzheimer's Disease.

PubMed

Lista, Simone; O'Bryant, Sid E; Blennow, Kaj; Dubois, Bruno; Hugon, Jacques; Zetterberg, Henrik; Hampel, Harald

2015-01-01

Most forms of Alzheimer's disease (AD) are sporadic (sAD) or inherited in a non-Mendelian fashion, and less than 1% of cases are autosomal-dominant. Forms of sAD do not exhibit familial aggregation and are characterized by complex genetic and environmental interactions. Recently, the expansion of genomic methodologies, in association with substantially larger combined cohorts, has resulted in various genome-wide association studies that have identified several novel genetic associations of AD. Currently, the most effective methods for establishing the diagnosis of AD are defined by multi-modal pathways, starting with clinical and neuropsychological assessment, cerebrospinal fluid (CSF) analysis, and brain-imaging procedures, all of which have significant cost- and access-to-care barriers. Consequently, research efforts have focused on the development and validation of non-invasive and generalizable blood-based biomarkers. Among the modalities conceptualized by the systems biology paradigm and utilized in the "exploratory biomarker discovery arena", proteome analysis has received the most attention. However, metabolomics, lipidomics, transcriptomics, and epigenomics have recently become key modalities in the search for AD biomarkers. Interestingly, biomarker changes for familial AD (fAD), in many but not all cases, seem similar to those for sAD. The integration of neurogenetics with systems biology/physiology-based strategies and high-throughput technologies for molecular profiling is expected to help identify the causes, mechanisms, and biomarkers associated with the various forms of AD. Moreover, in order to hypothesize the dynamic trajectories of biomarkers through disease stages and elucidate the mechanisms of biomarker alterations, updated and more sophisticated theoretical models have been proposed for both sAD and fAD.

Postmenopausal hormone therapy and Alzheimer disease: A prospective cohort study.

PubMed

Imtiaz, Bushra; Tuppurainen, Marjo; Rikkonen, Toni; Kivipelto, Miia; Soininen, Hilkka; Kröger, Heikki; Tolppanen, Anna-Maija

2017-03-14

To explore the association between postmenopausal hormone therapy (HT) and Alzheimer disease (AD). Twenty-year follow-up data from the Kuopio Osteoporosis Risk Factor and Prevention study cohort were used. Self-administered questionnaires were sent to all women aged 47-56 years, residing in Kuopio Province starting in 1989 until 2009, every 5th year. Register-based information on HT prescriptions was available since 1995. Probable AD cases, based on DSM-IV and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, were identified from the special reimbursement register (1999-2009). The study population included 8,195 women (227 cases of incident AD). Postmenopausal estrogen use was not associated with AD risk in register-based or self-reported data (hazard ratio/95% confidence interval 0.92/0.68-1.2, 0.99/0.75-1.3, respectively). Long-term self-reported postmenopausal HT was associated with reduced AD risk (0.53/0.31-0.91). Similar results were obtained with any dementia diagnosis in the hospital discharge register as an outcome. Our results do not provide strong evidence for a protective association between postmenopausal HT use and AD or dementia, although we observed a reduced AD risk among those with long-term self-reported HT use. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer's disease?

PubMed

Teipel, Stefan; Grothe, Michel J

2016-03-01

Posterior cingulate cortex (PCC) hypometabolism as measured by FDG PET is an indicator of Alzheimer's disease (AD) in prodromal stages, such as in mild cognitive impairment (MCI), and has been found to be closely associated with hippocampus atrophy in AD dementia. We studied the effects of local and remote atrophy and of local amyloid load on the PCC metabolic signal in patients with different preclinical and clinical stages of AD. We determined the volume of the hippocampus and PCC grey matter based on volumetric MRI scans, PCC amyloid load based on AV45 PET, and PCC metabolism based on FDG PET in 667 subjects participating in the Alzheimer's Disease Neuroimaging Initiative spanning the range from cognitively normal ageing through prodromal AD to AD dementia. In cognitively normal individuals and those with early MCI, PCC hypometabolism was exclusively associated with hippocampus atrophy, whereas in subjects with late MCI it was associated with both local and remote effects of atrophy as well as local amyloid load. In subjects with AD dementia, PCC hypometabolism was exclusively related to local atrophy. Our findings suggest that the effects of remote pathology on PCC hypometabolism decrease and the effects of local pathology increase from preclinical to clinical stages of AD, consistent with a progressive disconnection of the PCC from downstream cortical and subcortical brain regions.

Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample.

PubMed

Rademakers, Rosa; Cruts, Marc; Sleegers, Kristel; Dermaut, Bart; Theuns, Jessie; Aulchenko, Yurii; Weckx, Stefan; De Pooter, Tim; Van den Broeck, Marleen; Corsmit, Ellen; De Rijk, Peter; Del-Favero, Jurgen; van Swieten, John; van Duijn, Cornelia M; Van Broeckhoven, Christine

2005-10-01

We obtained conclusive linkage of Alzheimer disease (AD) with a candidate region of 19.7 cM at 7q36 in an extended multiplex family, family 1270, ascertained in a population-based study of early-onset AD in the northern Netherlands. Single-nucleotide polymorphism and haplotype association analyses of a Dutch patient-control sample further supported the linkage at 7q36. In addition, we identified a shared haplotype at 7q36 between family 1270 and three of six multiplex AD-affected families from the same geographical region, which is indicative of a founder effect and defines a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified one linked synonymous mutation, g.38030G-->C in exon 10, that affected codon 626 of the PAX transactivation domain interacting protein gene (PAXIP1). It remains to be determined whether PAXIP1 has a functional role in the expression of AD in family 1270 or whether another mutation at this locus explains the observed linkage and sharing. Together, our linkage data from the informative family 1270 and the association data in the population-based early-onset AD patient-control sample strongly support the identification of a novel AD locus at 7q36 and re-emphasize the genetic heterogeneity of AD.

Magnetic resonance imaging for monitoring therapeutic response in a transgenic mouse model of Alzheimer's disease using voxel-based analysis of amyloid plaques.

PubMed

Kim, Jae-Hun; Ha, Tae Lin; Im, Geun Ho; Yang, Jehoon; Seo, Sang Won; Chung, Julius Juhyun; Chae, Sun Young; Lee, In Su; Lee, Jung Hee

2014-03-05

In this study, we have shown the potential of a voxel-based analysis for imaging amyloid plaques and its utility in monitoring therapeutic response in Alzheimer's disease (AD) mice using manganese oxide nanoparticles conjugated with an antibody of Aβ1-40 peptide (HMON-abAβ40). T1-weighted MR brain images of a drug-treated AD group (n=7), a nontreated AD group (n=7), and a wild-type group (n=7) were acquired using a 7.0 T MRI system before (D-1), 24-h (D+1) after, and 72-h (D+3) after injection with an HMON-abAβ40 contrast agent. For the treatment of AD mice, DAPT was injected intramuscularly into AD transgenic mice (50 mg/kg of body weight). For voxel-based analysis, the skull-stripped mouse brain images were spatially normalized, and these voxels' intensities were corrected to reduce voxel intensity differences across scans in different mice. Statistical analysis showed higher normalized MR signal intensity in the frontal cortex and hippocampus of AD mice over wild-type mice on D+1 and D+3 (P<0.01, uncorrected for multiple comparisons). After the treatment of AD mice, the normalized MR signal intensity in the frontal cortex and hippocampus decreased significantly in comparison with nontreated AD mice on D+1 and D+3 (P<0.01, uncorrected for multiple comparisons). These results were confirmed by histological analysis using a thioflavin staining. This unique strategy allows us to detect brain regions that are subjected to amyloid plaque deposition and has the potential for human applications in monitoring therapeutic response for drug development in AD.

Adenovirus vector induced innate immune responses: impact upon efficacy and toxicity in gene therapy and vaccine applications.

PubMed

Hartman, Zachary C; Appledorn, Daniel M; Amalfitano, Andrea

2008-03-01

Extensively characterized, modified, and employed for a variety of purposes, adenovirus (Ad) vectors are generally regarded as having great potential by many applied virologists who wish to manipulate and use viral biology to achieve beneficial clinical outcomes. Despite widespread functional prominence and utility (i.e., Ad-based clinical trials have begun to progress to critical Phase III levels, it has recently become apparent that investigations regarding the innate immune response to Ads may reveal not only reasons behind previous failures, but also reveal novel insights that will allow for safer, more efficacious uses of this important gene transfer platform. Insights gained by the exploration of Ad induced innate immune responses will likely be most important to the fields of vaccine development, since Ad-based vaccines are regarded as one of the more promising vaccine platforms in development today. Adenovirus is currently known to interact with several different extracellular, intracellular, and membrane-bound innate immune sensing systems. Past and recent studies involving manipulation of the Ad infectious cycle as well as use of different mutants have shed light on some of the initiation mechanisms underlying Ad induced immune responses. More recent studies using microarray-based analyses, genetically modified cell lines and/or mouse mutants, and advanced generation Ad vectors have revealed important new insights into the scope and mechanism of this cellular defensive response. This review is an attempt to synthesize these studies, update Ad biologists to the current knowledge surrounding these increasingly important issues, as well as highlight areas where future research should be directed. It should also serve as a sobering reality to researchers exploring the use of any gene transfer vector, as to the complexities potentially involved when contemplating use of such vectors for human applications.

Adenovirus vector induced Innate Immune responses: Impact upon efficacy and toxicity in gene therapy and vaccine applications

PubMed Central

Hartman, Zachary C.; Appledorn, Daniel M.; Amalfitano, Andrea

2013-01-01

Extensively characterized, modified, and employed for a variety of purposes, Adenovirus (Ad) vectors are generally regarded as having great potential by many applied virologists who wish to manipulate and use viral biology to achieve beneficial clinical outcomes. Despite widespread functional prominence and utility, (i.e.: Ad based clinical trials have begun to progress to critical Phase III levels, it has recently become apparent that investigations regarding the innate immune response to Ads may reveal not only reasons behind previous failures, but also reveal novel insights that will allow for safer, more efficacious uses of this important gene transfer platform. Insights gained by the exploration of Ad induced innate immune responses will likely be most important to the fields of vaccine development, since Ad based vaccines are highly acknowledged as one of the more promising vaccine platforms in development today. Adenovirus is currently known to interact with several different extracellular, intracellular, and membrane bound innate immune sensing systems. Past and recent studies involving manipulation of the Ad infectious cycle as well as use of different mutants have shed light on some of the initiation mechanisms underlying Ad induced immune responses. More recent studies using microarray based analyses, genetically modified cell lines and/or mouse mutants, and advanced generation Ad vectors have revealed important new insights into the scope and mechanism of this cellular defensive response. This review is an attempt to synthesize these studies, update Ad biologists to the current knowledge surrounding these increasingly important issues, as well point areas where future research should be directed. It should also serve as a sobering reality to researchers exploring the use of any gene transfer vector, as to the complexities potentially involved when contemplating use of such vectors for human applications. PMID:18036698

A current view of Alzheimer's disease.

PubMed

Hooli, Basavaraj V; Tanzi, Rudolph E

2009-07-08

Several genes that influence susceptibility to Alzheimer's disease (AD) have been known for over two decades. Recent advances have elucidated novel candidate genes and the pathogenetic mechanisms underlying neurodegeneration in AD. Here, we summarize what we have learned from studies of the known AD genes with regard to the causes of AD and emerging therapies. We also review key recent discoveries that have enhanced our understanding of the etiology and pathogenesis of this devastating disease, based on new investigations into the genes and molecular mechanisms underlying AD.

26 CFR 1.164-3 - Definitions and special rules.

Code of Federal Regulations, 2014 CFR

2014-04-01

... proportion to the value of the personal property. A tax which is based on criteria other than value does not qualify as ad valorem. For example, a motor vehicle tax based on weight, model year, and horsepower, or any of these characteristics is not an ad valorem tax. However, a tax which is partly based on value...

26 CFR 1.164-3 - Definitions and special rules.

Code of Federal Regulations, 2012 CFR

2012-04-01

... proportion to the value of the personal property. A tax which is based on criteria other than value does not qualify as ad valorem. For example, a motor vehicle tax based on weight, model year, and horsepower, or any of these characteristics is not an ad valorem tax. However, a tax which is partly based on value...

26 CFR 1.164-3 - Definitions and special rules.

Code of Federal Regulations, 2013 CFR

2013-04-01

... proportion to the value of the personal property. A tax which is based on criteria other than value does not qualify as ad valorem. For example, a motor vehicle tax based on weight, model year, and horsepower, or any of these characteristics is not an ad valorem tax. However, a tax which is partly based on value...

Value-Added to What? How a Ceiling in the Testing Instrument Influences Value-Added Estimation. NBER Working Paper No. 14778

ERIC Educational Resources Information Center

Koedel, Cory; Betts, Julian

2009-01-01

Value-added measures of teacher quality may be sensitive to the quantitative properties of the student tests upon which they are based. This paper focuses on the sensitivity of value- added to test-score-ceiling effects. Test-score ceilings are increasingly common in testing instruments across the country as education policy continues to emphasize…

Multimerization of Adenovirus Serotype 3 Fiber Knob Domains Is Required for Efficient Binding of Virus to Desmoglein 2 and Subsequent Opening of Epithelial Junctions▿

PubMed Central

Wang, Hongjie; Li, ZongYi; Yumul, Roma; Lara, Stephanie; Hemminki, Akseli; Fender, Pascal; Lieber, André

2011-01-01

Recently, we identified desmoglein 2 (DSG2) as the main receptor for a group of species B adenoviruses (Ads), including Ad3, a serotype that is widely distributed in the human population (H. Wang et al., Nat. Med. 17:96–104, 2011). In this study, we have attempted to delineate structural details of the Ad3 interaction with DSG2. For CAR- and CD46-interacting Ad serotypes, attachment to cells can be completely blocked by an excess of recombinant fiber knob protein, while soluble Ad3 fiber knob only inefficiently blocks Ad3 infection. We found that the DSG2-interacting domain(s) within Ad3 is formed by several fiber knob domains that have to be in the spatial constellation that is present in viral particles. Based on this finding, we generated a small recombinant, self-dimerizing protein containing the Ad3 fiber knob (Ad3-K/S/Kn). Ad3-K/S/Kn bound to DSG2 with high affinity and blocked Ad3 infection. We demonstrated by confocal immunofluorescence and transmission electron microscopy analyses that Ad3-K/S/Kn, through its binding to DSG2, triggered the transient opening of intercellular junctions in epithelial cells. The pretreatment of epithelial cells with Ad3-K/S/Kn resulted in increased access to receptors that are localized in or masked by epithelial junctions, e.g., CAR or Her2/neu. Ad3-K/S/Kn treatment released CAR from tight junctions and thus increased the transduction of epithelial cells by a serotype Ad5-based vector. Furthermore, the pretreatment of Her2/neu-positive breast cancer cells with Ad3-K/S/Kn increased the killing of cancer cells by the Her2/neu-targeting monoclonal antibody trastuzumab (Herceptin). This study widens our understanding of how Ads achieve high avidity to their receptors and the infection of epithelial tissue. The small recombinant protein Ad3-K/S/Kn has practical implications for the therapy of epithelial cancer and gene/drug delivery to normal epithelial tissues. PMID:21525338

A Novel Virtual Reality-Based Training Protocol for the Enhancement of the "Mental Frame Syncing" in Individuals with Alzheimer's Disease: A Development-of-Concept Trial.

PubMed

Serino, Silvia; Pedroli, Elisa; Tuena, Cosimo; De Leo, Gianluca; Stramba-Badiale, Marco; Goulene, Karine; Mariotti, Noemi G; Riva, Giuseppe

2017-01-01

A growing body of evidence suggests that people with Alzheimer's Disease (AD) show compromised spatial abilities. In addition, there exists from the earliest stages of AD a specific impairment in "mental frame syncing," which is the ability to synchronize an allocentric viewpoint-independent representation (including object-to-object information) with an egocentric one by computing the bearing of each relevant "object" in the environment in relation to the stored heading in space (i.e., information about our viewpoint contained in the allocentric viewpoint-dependent representation). The main objective of this development-of-concept trial was to evaluate the efficacy of a novel VR-based training protocol focused on the enhancement of the "mental frame syncing" of the different spatial representations in subjects with AD. We recruited 20 individuals with AD who were randomly assigned to either "VR-based training" or "Control Group." Moreover, eight cognitively healthy elderly individuals were recruited to participate in the VR-based training in order to have a different comparison group. Based on a neuropsychological assessment, our results indicated a significant improvement in long-term spatial memory after the VR-based training for patients with AD; this means that transference of improvements from the VR-based training to more general aspects of spatial cognition was observed. Interestingly, there was also a significant effect of VR-based training on executive functioning for cognitively healthy elderly individuals. In sum, VR could be considered as an advanced embodied tool suitable for treating spatial recall impairments.

Biomarkers of Alzheimer’s Disease Among Mexican Americans

PubMed Central

O’Bryant, Sid E.; Xiao, Guanghua; Edwards, Melissa; Devous, Michael; Gupta, Veer Bala; Martins, Ralph; Zhang, Fan; Barber, Robert

2013-01-01

Background Mexican Americans are the fastest aging segment of the U.S. population yet little scientific literature exists regarding the Alzheimer disease (AD) among this segment of the population. The extant literature suggests that biomarkers of AD will vary according to race/ethnicity though no prior work has explicitly studied this possibility. The aim of this study was to create a serum-based biomarker profile of AD among Mexican American. Methods Data were analyzed from 363 Mexican American participants (49 AD and 314 normal controls) enrolled in the Texas Alzheimer’s Research & Care Consortium (TARCC). Non-fasting serum samples were analyzed using a luminex-based multi-plex platform. A biomarker profile was generated using random forest analyses. Results The biomarker profile of AD among Mexican Americans was different from prior work from non-Hispanic populations with regards to the variable importance plots. In fact, many of the top markers were related to metabolic factors (e.g. FABP, GLP-1, CD40, pancreatic polypeptide, insulin-like-growth factor, and insulin). The biomarker profile was a significant classifier of AD status yielding an area under the receiver operating characteristic curve (AUC), sensitivity (SN) and specificity (SP) of 0.77, 0.92 and 0.64, respectively. Combining biomarkers with clinical variables yielded a better balance of SN and SP. Conclusion The biomarker profile for AD among Mexican American cases is significantly different from that previously identified among non-Hispanic cases from many large-scale studies. This is the first study to explicitly examine and provide support for blood-based biomarkers of AD among Mexican Americans. Areas for future research are highlighted. PMID:23313927

Adenocarcinoma predominant pattern subtyping and nuclear grading in cytology: Is there a role in prognostication of advanced pulmonary adenocarcinomas?

PubMed

Nambirajan, A; Kaur, H; Jangra, K; Kaur, K; Madan, K; Mathur, S R; Iyer, V K; Jain, D

2018-04-01

Primary lung adenocarcinomas (ADs) show varied architectural patterns, and pattern-based subtyping of ADs is currently recommended due to prognostic implications. Predicting AD patterns on cytology is challenging; however, cytological nuclear features appear to correlate with histological grade and survival in early stage lung ADs. The feasibility and value of AD pattern prediction and nuclear grading on cytology in advanced lung ADs is not known. We aimed to predict patterns and analyse nuclear features on cytology and evaluate their role in prognostication. One-hundred patients of Stage III/IV lung AD with available matched cytology and histology samples were included. Cyto-patterns based on cell arrangement patterns (flat sheets vs three-dimensional clusters vs papillae) and cyto-nuclear score based on nuclear features (size, shape, contour), nucleoli (macronucleoli vs prominent vs inconspicuous), and nuclear chromatin were determined, and correlated with predominant histological-pattern observed on the matched small biopsy and outcome. Higher cyto-nuclear scores were observed with high-grade histo-patterns (solid, micropapillary and cribriform), while the predicted cyto-patterns did not correspond to the predominant pattern on histology in 77% cases. Highest cyto-histo agreement was observed for solid pattern (72%). High grade histo-patterns and cyto-nuclear scores > 3 showed a trend towards inferior survival (not significant). Nuclear grade scoring on cytology is simple to perform, and is predictive of high grade patterns. Its inclusion in routine reporting of cytology samples of lung ADs may be valuable. © 2018 John Wiley & Sons Ltd.

Packets Distributing Evolutionary Algorithm Based on PSO for Ad Hoc Network

NASA Astrophysics Data System (ADS)

Xu, Xiao-Feng

2018-03-01

Wireless communication network has such features as limited bandwidth, changeful channel and dynamic topology, etc. Ad hoc network has lots of difficulties in accessing control, bandwidth distribution, resource assign and congestion control. Therefore, a wireless packets distributing Evolutionary algorithm based on PSO (DPSO)for Ad Hoc Network is proposed. Firstly, parameters impact on performance of network are analyzed and researched to obtain network performance effective function. Secondly, the improved PSO Evolutionary Algorithm is used to solve the optimization problem from local to global in the process of network packets distributing. The simulation results show that the algorithm can ensure fairness and timeliness of network transmission, as well as improve ad hoc network resource integrated utilization efficiency.

Integrated Display and Simulation for Automatic Dependent Surveillance-Broadcast and Traffic Collision Avoidance System Data Fusion.

PubMed

Wang, Yanran; Xiao, Gang; Dai, Zhouyun

2017-11-13

Automatic Dependent Surveillance-Broadcast (ADS-B) is the direction of airspace surveillance development. Research analyzing the benefits of Traffic Collision Avoidance System (TCAS) and ADS-B data fusion is almost absent. The paper proposes an ADS-B minimum system from ADS-B In and ADS-B Out. In ADS-B In, a fusion model with a variable sampling Variational Bayesian-Interacting Multiple Model (VSVB-IMM) algorithm is proposed for integrated display and an airspace traffic situation display is developed by using ADS-B information. ADS-B Out includes ADS-B Out transmission based on a simulator platform and an Unmanned Aerial Vehicle (UAV) platform. This paper describes the overall implementation of ADS-B minimum system, including theoretical model design, experimental simulation verification, engineering implementation, results analysis, etc. Simulation and implementation results show that the fused system has better performance than each independent subsystem and it can work well in engineering applications.

A Model of Consumer Response to Over-the-Counter Drug Advertising: Antecedents and Influencing Factors.

PubMed

Huh, Jisu; Delorme, Denise E; Reid, Leonard N

2016-01-01

Given the importance of over-the-counter (OTC) drugs in the health care marketplace and lack of systematic research on OTC drug advertising (OTCA) effects, this study tested a theory-based, product category-specific OTCA effects model. Structural equation modeling analysis of data for 1 OTC drug category, analgesics, supported the proposed model, explaining the OTCA effect process from key consumer antecedents to ad involvement, from ad involvement to ad attention, from ad attention to cognitive responses, then to affective/evaluative responses, leading to the final behavioral outcome. Several noteworthy patterns also emerged: (a) Product involvement was directly linked to ad attention, rather than exerting an indirect influence through ad involvement; (b) ad attention was significantly related to both cognitive and affective/evaluative responses to different degrees, with stronger links to cognitive responses; and (c) ad-prompted actions were influenced by both ad trust and ad attitude.

High resolution A/D conversion based on piecewise conversion at lower resolution

DOEpatents

Terwilliger, Steve [Albuquerque, NM

2012-06-05

Piecewise conversion of an analog input signal is performed utilizing a plurality of relatively lower bit resolution A/D conversions. The results of this piecewise conversion are interpreted to achieve a relatively higher bit resolution A/D conversion without sampling frequency penalty.

Effects of a self-guided, web-based activity programme for patients with persistent musculoskeletal pain in primary healthcare: A randomized controlled trial.

PubMed

Calner, T; Nordin, C; Eriksson, M K; Nyberg, L; Gard, G; Michaelson, P

2017-07-01

Web-based interventions for pain management are increasingly used with possible benefits, but never used in addition to multimodal rehabilitation (MMR). MMR is recommended treatment for persistent pain in Sweden. The aim was to evaluate the effects of a self-guided, web-based programme added to MMR for work ability, pain, disability and health-related quality of life. We included 99 participants with persistent musculoskeletal pain in a randomized study with two intervention arms: (1) MMR and web-based intervention, and (2) MMR. Data was collected at baseline, 4 and 12 months. Outcome measures were work ability, working percentage, average pain intensity, pain-related disability, and health-related quality of life. There were no significant effects of adding the web-based intervention to MMR regarding any of the outcome variables. This trial provides no support for adding a self-guided, web-based activity programme to MMR for patients with persistent musculoskeletal pain. The comprehensive self-guided, web-based programme for activity, Web-BCPA, added to multimodal treatment in primary health care had no effect on work ability, pain, disability or health-related quality of life. Future web-based interventions should be tailored to patients' individual needs and expectations. © 2017 European Pain Federation - EFIC®.

Automated detection of brain atrophy patterns based on MRI for the prediction of Alzheimer's disease

PubMed Central

Plant, Claudia; Teipel, Stefan J.; Oswald, Annahita; Böhm, Christian; Meindl, Thomas; Mourao-Miranda, Janaina; Bokde, Arun W.; Hampel, Harald; Ewers, Michael

2010-01-01

Subjects with mild cognitive impairment (MCI) have an increased risk to develop Alzheimer's disease (AD). Voxel-based MRI studies have demonstrated that widely distributed cortical and subcortical brain areas show atrophic changes in MCI, preceding the onset of AD-type dementia. Here we developed a novel data mining framework in combination with three different classifiers including support vector machine (SVM), Bayes statistics, and voting feature intervals (VFI) to derive a quantitative index of pattern matching for the prediction of the conversion from MCI to AD. MRI was collected in 32 AD patients, 24 MCI subjects and 18 healthy controls (HC). Nine out of 24 MCI subjects converted to AD after an average follow-up interval of 2.5 years. Using feature selection algorithms, brain regions showing the highest accuracy for the discrimination between AD and HC were identified, reaching a classification accuracy of up to 92%. The extracted AD clusters were used as a search region to extract those brain areas that are predictive of conversion to AD within MCI subjects. The most predictive brain areas included the anterior cingulate gyrus and orbitofrontal cortex. The best prediction accuracy, which was cross-validated via train-and-test, was 75% for the prediction of the conversion from MCI to AD. The present results suggest that novel multivariate methods of pattern matching reach a clinically relevant accuracy for the a priori prediction of the progression from MCI to AD. PMID:19961938

Association between added sugar intake and dental caries in Yup'ik children using a novel hair biomarker.

PubMed

Chi, Donald L; Hopkins, Scarlett; O'Brien, Diane; Mancl, Lloyd; Orr, Eliza; Lenaker, Dane

2015-10-09

Dental caries (tooth decay) is a significant public health problem in Alaska Native children. Dietary added sugars are considered one of the main risk factors. In this cross-sectional pilot study, we used a validated hair-based biomarker to measure added sugar intake in Alaska Native Yup'ik children ages 6-17 years (N = 51). We hypothesized that added sugar intake would be positively associated with tooth decay. A 66-item parent survey was administered, a hair sample was collected from each child, and a dental exam was conducted. Added sugar intake (grams/day) was measured from hair samples using a linear combination of carbon and nitrogen ratios. We used linear and log-linear regression models with robust standard errors to test our hypothesis that children with higher added sugar intake would have a higher proportion of carious tooth surfaces. The mean proportion of carious tooth surfaces was 30.8 % (standard deviation: 23.2 %). Hair biomarker-based added sugar intake was associated with absolute (6.4 %; 95 % CI: 1.2 %, 11.6 %; P = .02) and relative increases in the proportion of carious tooth surfaces (24.2 %; 95 % CI: 10.6 %, 39.4 %; P < .01). There were no associations between self-reported measures of sugar-sweetened food and beverage intake and tooth decay. Added sugar intake as assessed by hair biomarker was significantly and positively associated with tooth decay in our sample of Yup'ik children. Self-reported dietary measures were not associated tooth decay. Most added sugars were from sugar-sweetened fruit drinks consumed at home. Future dietary interventions aimed at improving the oral health of Alaska Native children should consider use of objective biomarkers to assess and measure changes in home-based added sugar intake, particularly sugar-sweetened fruit drinks.

Brick walls and AdS/CFT

NASA Astrophysics Data System (ADS)

Kay, Bernard S.; Ortíz, L.

2014-05-01

We discuss the relationship between the bulk-boundary correspondence in Rehren's algebraic holography (and in other `fixed-background', QFT-based, approaches to holography) and in mainstream string-theoretic `Maldacena AdS/CFT'. Especially, we contrast the understanding of black-hole entropy from the point of view of QFT in curved spacetime—in the framework of 't Hooft's `brick wall' model—with the understanding based on Maldacena AdS/CFT. We show that the brick-wall modification of a Klein-Gordon field in the Hartle-Hawking-Israel state on dimensional Schwarzschild AdS has a well-defined boundary limit with the same temperature and entropy as the brick-wall-modified bulk theory. One of our main purposes is to point out a close connection, for general AdS/CFT situations, between the puzzle raised by Arnsdorf and Smolin regarding the relationship between Rehren's algebraic holography and mainstream AdS/CFT and the puzzle embodied in the `complementarity principle' proposed by Mukohyama and Israel in their work on the brick-wall approach to black hole entropy. Working on the assumption that similar results will hold for bulk QFT other than the Klein-Gordon field and for Schwarzschild AdS in other dimensions, and recalling the first author's proposed resolution to the Mukohyama-Israel puzzle based on his `matter-gravity entanglement hypothesis', we argue that, in Maldacena AdS/CFT, the algebra of the boundary CFT is isomorphic only to a proper subalgebra of the bulk algebra, albeit (at non-zero temperature) the (GNS) Hilbert spaces of bulk and boundary theories are still the `same'—the total bulk state being pure, while the boundary state is mixed (thermal). We also argue from the finiteness of its boundary (and hence, on our assumptions, also bulk) entropy at finite temperature, that the Rehren dual of the Maldacena boundary CFT cannot itself be a QFT and must, instead, presumably be something like a string theory.

Alzheimer's disease prevention: from risk factors to early intervention.

PubMed

Crous-Bou, Marta; Minguillón, Carolina; Gramunt, Nina; Molinuevo, José Luis

2017-09-12

Due to the progressive aging of the population, Alzheimer's disease (AD) is becoming a healthcare burden of epidemic proportions for which there is currently no cure. Disappointing results from clinical trials performed in mild-moderate AD dementia combined with clear epidemiological evidence on AD risk factors are contributing to the development of primary prevention initiatives. In addition, the characterization of the long asymptomatic stage of AD is allowing the development of intervention studies and secondary prevention programmes on asymptomatic at-risk individuals, before substantial irreversible neuronal dysfunction and loss have occurred, an approach that emerges as highly relevant.In this manuscript, we review current strategies for AD prevention, from primary prevention strategies based on identifying risk factors and risk reduction, to secondary prevention initiatives based on the early detection of the pathophysiological hallmarks and intervention at the preclinical stage of the disease. Firstly, we summarize the evidence on several AD risk factors, which are the rationale for the establishment of primary prevention programmes as well as revising current primary prevention strategies. Secondly, we review the development of public-private partnerships for disease prevention that aim to characterize the AD continuum as well as serving as platforms for secondary prevention trials. Finally, we summarize currently ongoing clinical trials recruiting participants with preclinical AD or a higher risk for the onset of AD-related cognitive impairment.The growing body of research on the risk factors for AD and its preclinical stage is favouring the development of AD prevention programmes that, by delaying the onset of Alzheimer's dementia for only a few years, would have a huge impact on public health.

Effects of distinctive encoding on source-based false recognition: further examination of recall-to-reject processes in aging and Alzheimer disease.

PubMed

Pierce, Benton H; Waring, Jill D; Schacter, Daniel L; Budson, Andrew E

2008-09-01

To examine the use of distinctive materials at encoding on recall-to-reject monitoring processes in aging and Alzheimer disease (AD). AD patients, and to a lesser extent older adults, have shown an impaired ability to use recollection-based monitoring processes (eg, recall-to-reject) to avoid various types of false memories, such as source-based false recognition. Younger adults, healthy older adults, and AD patients engaged in an incidental learning task, in which critical category exemplars were either accompanied by a distinctive picture or were presented as only words. Later, participants studied a series of categorized lists in which several typical exemplars were omitted and were then given a source memory test. Both older and younger adults made more accurate source attributions after picture encoding compared with word-only encoding, whereas AD patients did not exhibit this distinctiveness effect. These results extend those of previous studies showing that monitoring in older adults can be enhanced with distinctive encoding, and suggest that such monitoring processes in AD patients many be insensitive to distinctiveness.

Current Advances and Future Challenges in Adenoviral Vector Biology and Targeting

PubMed Central

Campos, Samuel K.; Barry, Michael A.

2008-01-01

Gene delivery vectors based on Adenoviral (Ad) vectors have enormous potential for the treatment of both hereditary and acquired disease. Detailed structural analysis of the Ad virion, combined with functional studies has broadened our knowledge of the structure/function relationships between Ad vectors and host cells/tissues and substantial achievement has been made towards a thorough understanding of the biology of Ad vectors. The widespread use of Ad vectors for clinical gene therapy is compromised by their inherent immunogenicity. The generation of safer and more effective Ad vectors, targeted to the site of disease, has therefore become a great ambition in the field of Ad vector development. This review provides a synopsis of the structure/function relationships between Ad vectors and host systems and summarizes the many innovative approaches towards achieving Ad vector targeting. PMID:17584037

Risk stratification for arrhythmic death in an emergency department cohort: a new method of nonlinear PD2i analysis of the ECG

PubMed Central

Skinner, James E; Meyer, Michael; Dalsey, William C; Nester, Brian A; Ramalanjaona, George; O’Neil, Brian J; Mangione, Antoinette; Terregino, Carol; Moreyra, Abel; Weiss, Daniel N; Anchin, Jerry M; Geary, Una; Taggart, Pamela

2008-01-01

Heart rate variability (HRV) reflects both cardiac autonomic function and risk of sudden arrhythmic death (AD). Indices of HRV based on linear stochastic models are independent risk factors for AD in postmyocardial infarction (MI) cohorts. Indices based on nonlinear deterministic models have a higher sensitivity and specificity for predicting AD in retrospective data. A new nonlinear deterministic model, the automated Point Correlation Dimension (PD2i), was prospectively evaluated for prediction of AD. Patients were enrolled (N = 918) in 6 emergency departments (EDs) upon presentation with chest pain and being determined to be at risk of acute MI (AMI) >7%. Brief digital ECGs (>1000 heartbeats, ∼15 min) were recorded and automated PD2i results obtained. Out-of-hospital AD was determined by modified Hinkle-Thaler criteria. All-cause mortality at 1 year was 6.2%, with 3.5% being ADs. Of the AD fatalities, 34% were without previous history of MI or diagnosis of AMI. The PD2i prediction of AD had sensitivity = 96%, specificity = 85%, negative predictive value = 99%, and relative risk >24.2 (p ≤ 0.001). HRV analysis by the time-dependent nonlinear PD2i algorithm can accurately predict risk of AD in an ED cohort and may have both life-saving and resource-saving implications for individual risk assessment. PMID:19209249

Longitudinal changes in microstructural white matter metrics in Alzheimer's disease.

PubMed

Mayo, Chantel D; Mazerolle, Erin L; Ritchie, Lesley; Fisk, John D; Gawryluk, Jodie R

2017-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current avenues of AD research focus on pre-symptomatic biomarkers that will assist with early diagnosis of AD. The majority of magnetic resonance imaging (MRI) based biomarker research to date has focused on neuronal loss in grey matter and there is a paucity of research on white matter. Longitudinal DTI data from the Alzheimer's Disease Neuroimaging Initiative 2 database were used to examine 1) the within-group microstructural white matter changes in individuals with AD and healthy controls at baseline and year one; and 2) the between-group microstructural differences in individuals with AD and healthy controls at both time points. 1) Within-group: longitudinal Tract-Based Spatial Statistics revealed that individuals with AD and healthy controls both had widespread reduced fractional anisotropy (FA) and increased mean diffusivity (MD) with changes in the hippocampal cingulum exclusive to the AD group. 2) Between-group: relative to healthy controls, individuals with AD had lower FA and higher MD in the hippocampal cingulum, as well as the corpus callosum, internal and external capsule; corona radiata; posterior thalamic radiation; superior and inferior longitudinal fasciculus; fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; and tapetum. The current results indicate that sensitivity to white matter microstructure is a promising avenue for AD biomarker research. Additional longitudinal studies on both white and grey matter are warranted to further evaluate potential clinical utility.

Nanotechnology-based drug delivery systems for Alzheimer's disease management: Technical, industrial, and clinical challenges.

PubMed

Wen, Ming Ming; El-Salamouni, Noha S; El-Refaie, Wessam M; Hazzah, Heba A; Ali, Mai M; Tosi, Giovanni; Farid, Ragwa M; Blanco-Prieto, Maria J; Billa, Nashiru; Hanafy, Amira S

2017-01-10

Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes. Despite extensive research, literature screening revealed that clinical activities involving NTDDS application in research for AD are lagging compared to NTDDS for other diseases such as cancers. The industrial perspectives, processability, and cost/benefit ratio of using NTDDS for AD treatment are usually overlooked. Moreover, active and passive immunization against AD are by far the mostly studied alternative AD therapies because conventional oral drug therapy is not yielding satisfactorily results. NTDDS of approved drugs appear promising to transform this research from 'paper to clinic' and raise hope for AD sufferers and their caretakers. This review summarizes the recent studies conducted on NTDDS for AD treatment, with a primary focus on the industrial perspectives and processability. Additionally, it highlights the ongoing clinical trials for AD management. Copyright © 2016 Elsevier B.V. All rights reserved.

76 FR 37774 - Announcement of Value-Added Producer Grant Application Deadlines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

...-Based Business Ventures develop strategies to create marketing opportunities and to help develop Business Plans for viable marketing opportunities regarding production of bio-based products from... Capital Grants directly related to the processing and/or marketing of value-added products. In order to...

Morphological hippocampal markers for automated detection of Alzheimer's disease and mild cognitive impairment converters in magnetic resonance images.

PubMed

Ferrarini, Luca; Frisoni, Giovanni B; Pievani, Michela; Reiber, Johan H C; Ganzola, Rossana; Milles, Julien

2009-01-01

In this study, we investigated the use of hippocampal shape-based markers for automatic detection of Alzheimer's disease (AD) and mild cognitive impairment converters (MCI-c). Three-dimensional T1-weighted magnetic resonance images of 50 AD subjects, 50 age-matched controls, 15 MCI-c, and 15 MCI-non-converters (MCI-nc) were taken. Manual delineations of both hippocampi were obtained from normalized images. Fully automatic shape modeling was used to generate comparable meshes for both structures. Repeated permutation tests, run over a randomly sub-sampled training set (25 controls and 25 ADs), highlighted shape-based markers, mostly located in the CA1 sector, which consistently discriminated ADs and controls. Support vector machines (SVMs) were trained, using markers from either one or both hippocampi, to automatically classify control and AD subjects. Leave-1-out cross-validations over the remaining 25 ADs and 25 controls resulted in an optimal accuracy of 90% (sensitivity 92%), for markers in the left hippocampus. The same morphological markers were used to train SVMs for MCI-c versus MCI-nc classification: markers in the right hippocampus reached an accuracy (and sensitivity) of 80%. Due to the pattern recognition framework, our results statistically represent the expected performances of clinical set-ups, and compare favorably to analyses based on hippocampal volumes.

Application of Machine Learning in Postural Control Kinematics for the Diagnosis of Alzheimer's Disease

PubMed Central

Yelshyna, Darya; Bicho, Estela

2016-01-01

The use of wearable devices to study gait and postural control is a growing field on neurodegenerative disorders such as Alzheimer's disease (AD). In this paper, we investigate if machine-learning classifiers offer the discriminative power for the diagnosis of AD based on postural control kinematics. We compared Support Vector Machines (SVMs), Multiple Layer Perceptrons (MLPs), Radial Basis Function Neural Networks (RBNs), and Deep Belief Networks (DBNs) on 72 participants (36 AD patients and 36 healthy subjects) exposed to seven increasingly difficult postural tasks. The decisional space was composed of 18 kinematic variables (adjusted for age, education, height, and weight), with or without neuropsychological evaluation (Montreal cognitive assessment (MoCA) score), top ranked in an error incremental analysis. Classification results were based on threefold cross validation of 50 independent and randomized runs sets: training (50%), test (40%), and validation (10%). Having a decisional space relying solely on postural kinematics, accuracy of AD diagnosis ranged from 71.7 to 86.1%. Adding the MoCA variable, the accuracy ranged between 91 and 96.6%. MLP classifier achieved top performance in both decisional spaces. Having comprehended the interdynamic interaction between postural stability and cognitive performance, our results endorse machine-learning models as a useful tool for computer-aided diagnosis of AD based on postural control kinematics. PMID:28074090

Application of Machine Learning in Postural Control Kinematics for the Diagnosis of Alzheimer's Disease.

PubMed

Costa, Luís; Gago, Miguel F; Yelshyna, Darya; Ferreira, Jaime; David Silva, Hélder; Rocha, Luís; Sousa, Nuno; Bicho, Estela

2016-01-01

The use of wearable devices to study gait and postural control is a growing field on neurodegenerative disorders such as Alzheimer's disease (AD). In this paper, we investigate if machine-learning classifiers offer the discriminative power for the diagnosis of AD based on postural control kinematics. We compared Support Vector Machines (SVMs), Multiple Layer Perceptrons (MLPs), Radial Basis Function Neural Networks (RBNs), and Deep Belief Networks (DBNs) on 72 participants (36 AD patients and 36 healthy subjects) exposed to seven increasingly difficult postural tasks. The decisional space was composed of 18 kinematic variables (adjusted for age, education, height, and weight), with or without neuropsychological evaluation (Montreal cognitive assessment (MoCA) score), top ranked in an error incremental analysis. Classification results were based on threefold cross validation of 50 independent and randomized runs sets: training (50%), test (40%), and validation (10%). Having a decisional space relying solely on postural kinematics, accuracy of AD diagnosis ranged from 71.7 to 86.1%. Adding the MoCA variable, the accuracy ranged between 91 and 96.6%. MLP classifier achieved top performance in both decisional spaces. Having comprehended the interdynamic interaction between postural stability and cognitive performance, our results endorse machine-learning models as a useful tool for computer-aided diagnosis of AD based on postural control kinematics.

Projected asymmetric response of Adélie penguins to Antarctic climate change

NASA Astrophysics Data System (ADS)

Cimino, Megan A.; Lynch, Heather J.; Saba, Vincent S.; Oliver, Matthew J.

2016-06-01

The contribution of climate change to shifts in a species’ geographic distribution is a critical and often unresolved ecological question. Climate change in Antarctica is asymmetric, with cooling in parts of the continent and warming along the West Antarctic Peninsula (WAP). The Adélie penguin (Pygoscelis adeliae) is a circumpolar meso-predator exposed to the full range of Antarctic climate and is undergoing dramatic population shifts coincident with climate change. We used true presence-absence data on Adélie penguin breeding colonies to estimate past and future changes in habitat suitability during the chick-rearing period based on historic satellite observations and future climate model projections. During the contemporary period, declining Adélie penguin populations experienced more years with warm sea surface temperature compared to populations that are increasing. Based on this relationship, we project that one-third of current Adélie penguin colonies, representing ~20% of their current population, may be in decline by 2060. However, climate model projections suggest refugia may exist in continental Antarctica beyond 2099, buffering species-wide declines. Climate change impacts on penguins in the Antarctic will likely be highly site specific based on regional climate trends, and a southward contraction in the range of Adélie penguins is likely over the next century.

Antibody-Mimetic Peptoid Nanosheet for Label-Free Serum-Based Diagnosis of Alzheimer's Disease.

PubMed

Zhu, Ling; Zhao, Zijian; Cheng, Peng; He, Zhaohui; Cheng, Zhiqiang; Peng, Jiaxi; Wang, Huayi; Wang, Chen; Yang, Yanlian; Hu, Zhiyuan

2017-08-01

Alzheimer's disease (AD) is the most common form of dementia characterized by progressive cognitive decline. Current diagnosis of AD is based on symptoms, neuropsychological tests, and neuroimaging, and is usually evident years after the pathological process. Early assessment at the preclinical or prodromal stage is in a great demand since treatment after the onset can hardly stop or reverse the disease progress. However, early diagnosis of AD is challenging due to the lack of reliable noninvasive approaches. Here, an antibody-mimetic self-assembling peptoid nanosheet containing surface-exposed Aβ42-recognizing loops is constructed, and a label-free sensor for the detection of AD serum is developed. The loop-displaying peptoid nanosheet is demonstrated to have high affinity to serum Aβ42, and to be able to identify AD sera with high sensitivity. The dense distribution of molecular recognition loops on the robust peptoid nanosheet scaffold not only mimics the architecture of antibodies, but also reduces the nonspecific binding in detecting multicomponent samples. This antibody-mimetic 2D material holds great potential toward the blood-based diagnosis of AD, and meanwhile provides novel insights into the antibody alternative engineering and the universal application in biological and chemical sensors. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Attitude determination for small satellites using GPS signal-to-noise ratio

NASA Astrophysics Data System (ADS)

Peters, Daniel

An embedded system for GPS-based attitude determination (AD) using signal-to-noise (SNR) measurements was developed for CubeSat applications. The design serves as an evaluation testbed for conducting ground based experiments using various computational methods and antenna types to determine the optimum AD accuracy. Raw GPS data is also stored to non-volatile memory for downloading and post analysis. Two low-power microcontrollers are used for processing and to display information on a graphic screen for real-time performance evaluations. A new parallel inter-processor communication protocol was developed that is faster and uses less power than existing standard protocols. A shorted annular patch (SAP) antenna was fabricated for the initial ground-based AD experiments with the testbed. Static AD estimations with RMS errors in the range of 2.5° to 4.8° were achieved over a range of off-zenith attitudes.

A community-based approach to trials of aerobic exercise in aging and Alzheimer’s disease

PubMed Central

Vidoni, Eric D.; Van Sciver, Angela; Johnson, David K.; He, Jinghua; Honea, Robyn; Haines, Brian; Goodwin, Jami; Laubinger, M. Pat; Anderson, Heather S.; Kluding, Patricia M.; Donnelly, Joseph E.; Billinger, Sandra A.; Burns, Jeffrey M.

2012-01-01

The benefits of exercise for aging have received considerable attention in both the popular and academic press. The putative benefits of exercise for maximizing cognitive function and supporting brain health have great potential for combating Alzheimer’s disease (AD). Aerobic exercise offers a low-cost, low-risk intervention that is widely available and may have disease modifying effects. Demonstrating aerobic exercise alters the AD process would have enormous public health implications. The purpose of this paper is to a report the protocol of a current, community-based pilot study of aerobic exercise for AD to guide future investigation. This manuscript provides 1) an overview of possible benefits of exercise in those with dementia, 2) a rationale and recommendations for implementation of a community-based approach, 3) recommendation for implementation of similar study protocols, 4) unique challenges in conducting an exercise trial in AD. PMID:22903151

Nitrogen transformations in a waterhyacinth-based water treatment system. [Eichornia crassipes (Mart. ) Solms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moorhead, K.K.; Reddy, K.R.; Graetz, D.A.

Fate of added /sup 15/NH/sub 4/-N and /sup 15/NO/sub 3/-N in waterhyacinth (Eichhornia crassipes (Mart.) Solms)-based water treatment system was evaluated under controlled conditions. Labeled /sup 15/NH/sub 4/-N uptake by waterhyacinth exceeded /sup 15/NO/sub 3/-N uptake. Total /sup 15/N recovery by waterhyacinth ranged from 57 to 72% for added /sup 15/NO/sub 3/-N and 70 to 89% for added /sup 15/NH/sub 4/-N. Both sediment and detritus were potential sources of N for waterhyacinths. Waterhyacinths cultured in sewage effluent removed 55% of the added /sup 15/NH/sub 4/-N and 14% of the added /sup 15/NO/sub 3/-N, respectively. Three to 44% of the addedmore » /sup 15/NH/sub 4/-N was lost through nitrification in the water column and subsequent denitrification in the underlying sediments, whereas 24 to 86% of the added /sup 15/NO/sub 3/-N was lost through denitrification. In a system without plants, 13 to 89% of the added /sup 15/NH/sub 4/-N and 48 to 96% of the added /sup 15/NO/sub 3/-N were lost from the system through a combination of nitrification/denitrification and NH/sub 3/ volatilization.« less

MEG connectivity analysis in patients with Alzheimer's disease using cross mutual information and spectral coherence.

PubMed

Alonso, Joan Francesc; Poza, Jesús; Mañanas, Miguel Angel; Romero, Sergio; Fernández, Alberto; Hornero, Roberto

2011-01-01

Alzheimer's disease (AD) is an irreversible brain disorder which represents the most common form of dementia in western countries. An early and accurate diagnosis of AD would enable to develop new strategies for managing the disease; however, nowadays there is no single test that can accurately predict the development of AD. In this sense, only a few studies have focused on the magnetoencephalographic (MEG) AD connectivity patterns. This study compares brain connectivity in terms of linear and nonlinear couplings by means of spectral coherence and cross mutual information function (CMIF), respectively. The variables defined from these functions provide statistically significant differences (p < 0.05) between AD patients and control subjects, especially the variables obtained from CMIF. The results suggest that AD is characterized by both decreases and increases of functional couplings in different frequency bands as well as by an increase in regularity, that is, more evident statistical deterministic relationships in AD patients' MEG connectivity. The significant differences obtained indicate that AD could disturb brain interactions causing abnormal brain connectivity and operation. Furthermore, the combination of coherence and CMIF features to perform a diagnostic test based on logistic regression improved the tests based on individual variables for its robustness.

Individual Patient Diagnosis of AD and FTD via High-Dimensional Pattern Classification of MRI

PubMed Central

Davatzikos, C.; Resnick, S. M.; Wu, X.; Parmpi, P.; Clark, C. M.

2008-01-01

The purpose of this study is to determine the diagnostic accuracy of MRI-based high-dimensional pattern classification in differentiating between patients with Alzheimer’s Disease (AD), Frontotemporal Dementia (FTD), and healthy controls, on an individual patient basis. MRI scans of 37 patients with AD and 37 age-matched cognitively normal elderly individuals, as well as 12 patients with FTD and 12 age-matched cognitively normal elderly individuals, were analyzed using voxel-based analysis and high-dimensional pattern classification. Diagnostic sensitivity and specificity of spatial patterns of regional brain atrophy found to be characteristic of AD and FTD were determined via cross-validation and via split-sample methods. Complex spatial patterns of relatively reduced brain volumes were identified, including temporal, orbitofrontal, parietal and cingulate regions, which were predominantly characteristic of either AD or FTD. These patterns provided 100% diagnostic accuracy, when used to separate AD or FTD from healthy controls. The ability to correctly distinguish AD from FTD averaged 84.3%. All estimates of diagnostic accuracy were determined via cross-validation. In conclusion, AD- and FTD-specific patterns of brain atrophy can be detected with high accuracy using high-dimensional pattern classification of MRI scans obtained in a typical clinical setting. PMID:18474436

Independent component analysis of DTI data reveals white matter covariances in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Ouyang, Xin; Sun, Xiaoyu; Guo, Ting; Sun, Qiaoyue; Chen, Kewei; Yao, Li; Wu, Xia; Guo, Xiaojuan

2014-03-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease with the clinical symptom of the continuous deterioration of cognitive and memory functions. Multiple diffusion tensor imaging (DTI) indices such as fractional anisotropy (FA) and mean diffusivity (MD) can successfully explain the white matter damages in AD patients. However, most studies focused on the univariate measures (voxel-based analysis) to examine the differences between AD patients and normal controls (NCs). In this investigation, we applied a multivariate independent component analysis (ICA) to investigate the white matter covariances based on FA measurement from DTI data in 35 AD patients and 45 NCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We found that six independent components (ICs) showed significant FA reductions in white matter covariances in AD compared with NC, including the genu and splenium of corpus callosum (IC-1 and IC-2), middle temporal gyral of temporal lobe (IC-3), sub-gyral of frontal lobe (IC-4 and IC-5) and sub-gyral of parietal lobe (IC-6). Our findings revealed covariant white matter loss in AD patients and suggest that the unsupervised data-driven ICA method is effective to explore the changes of FA in AD. This study assists us in understanding the mechanism of white matter covariant reductions in the development of AD.

Ensemble based on static classifier selection for automated diagnosis of Mild Cognitive Impairment.

PubMed

Nanni, Loris; Lumini, Alessandra; Zaffonato, Nicolò

2018-05-15

Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia in the elderly population. Scientific research is very active in the challenge of designing automated approaches to achieve an early and certain diagnosis. Recently an international competition among AD predictors has been organized: "A Machine learning neuroimaging challenge for automated diagnosis of Mild Cognitive Impairment" (MLNeCh). This competition is based on pre-processed sets of T1-weighted Magnetic Resonance Images (MRI) to be classified in four categories: stable AD, individuals with MCI who converted to AD, individuals with MCI who did not convert to AD and healthy controls. In this work, we propose a method to perform early diagnosis of AD, which is evaluated on MLNeCh dataset. Since the automatic classification of AD is based on the use of feature vectors of high dimensionality, different techniques of feature selection/reduction are compared in order to avoid the curse-of-dimensionality problem, then the classification method is obtained as the combination of Support Vector Machines trained using different clusters of data extracted from the whole training set. The multi-classifier approach proposed in this work outperforms all the stand-alone method tested in our experiments. The final ensemble is based on a set of classifiers, each trained on a different cluster of the training data. The proposed ensemble has the great advantage of performing well using a very reduced version of the data (the reduction factor is more than 90%). The MATLAB code for the ensemble of classifiers will be publicly available 1 to other researchers for future comparisons. Copyright © 2017 Elsevier B.V. All rights reserved.

Discerning mild cognitive impairment and Alzheimer Disease from normal aging: morphologic characterization based on univariate and multivariate models.

PubMed

Liao, Weiqi; Long, Xiaojing; Jiang, Chunxiang; Diao, Yanjun; Liu, Xin; Zheng, Hairong; Zhang, Lijuan

2014-05-01

Differentiating mild cognitive impairment (MCI) and Alzheimer Disease (AD) from healthy aging remains challenging. This study aimed to explore the cerebral structural alterations of subjects with MCI or AD as compared to healthy elderly based on the individual and collective effects of cerebral morphologic indices using univariate and multivariate analyses. T1-weighted images (T1WIs) were retrieved from Alzheimer Disease Neuroimaging Initiative database for 116 subjects who were categorized into groups of healthy aging, MCI, and AD. Analysis of covariance (ANCOVA) and multivariate analysis of covariance (MANCOVA) were performed to explore the intergroup morphologic alterations indexed by surface area, curvature index, cortical thickness, and subjacent white matter volume with age and sex controlled as covariates, in 34 parcellated gyri regions of interest (ROIs) for both cerebral hemispheres based on the T1WI. Statistical parameters were mapped on the anatomic images to facilitate visual inspection. Global rather than region-specific structural alterations were revealed in groups of MCI and AD relative to healthy elderly using MANCOVA. ANCOVA revealed that the cortical thickness decreased more prominently in entorhinal, temporal, and cingulate cortices and was positively correlated with patients' cognitive performance in AD group but not in MCI. The temporal lobe features marked atrophy of white matter during the disease dynamics. Significant intercorrelations were observed among the morphologic indices with univariate analysis for given ROIs. Significant global structural alterations were identified in MCI and AD based on MANCOVA model with improved sensitivity. The intercorrelation among the morphologic indices may dampen the use of individual morphological parameter in featuring cerebral structural alterations. Decrease in cortical thickness is not reflective of the cognitive performance at the early stage of AD. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Prospective Memory Impairments in Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia: Clinical and Neural Correlates.

PubMed

Dermody, Nadene; Hornberger, Michael; Piguet, Olivier; Hodges, John R; Irish, Muireann

2016-01-01

Prospective memory (PM) refers to a future-oriented form of memory in which the individual must remember to execute an intended action either at a future point in time (Time-based) or in response to a specific event (Event-based). Lapses in PM are commonly exhibited in neurodegenerative disorders including Alzheimer's disease (AD) and frontotemporal dementia (FTD), however, the neurocognitive mechanisms driving these deficits remain unknown. To investigate the clinical and neural correlates of Time- and Event-based PM disruption in AD and the behavioral-variant FTD (bvFTD). Twelve AD, 12 bvFTD, and 12 healthy older Control participants completed a modified version of the Cambridge Prospective Memory test, which examines Time- and Event-based aspects of PM. All participants completed a standard neuropsychological assessment and underwent whole-brain structural MRI. AD and bvFTD patients displayed striking impairments across Time- and Event-based PM relative to Controls, however, Time-based PM was disproportionately affected in the AD group. Episodic memory dysfunction and hippocampal atrophy were found to correlate strongly with PM integrity in both patient groups, however, dissociable neural substrates were also evident for PM performance across dementia syndromes. Our study reveals the multifaceted nature of PM dysfunction in neurodegenerative disorders, and suggests common and dissociable neurocognitive mechanisms, which subtend these deficits in each patient group. Future studies of PM disturbance in dementia syndromes will be crucial for the development of successful interventions to improve functional independence in the patient's daily life.

Fabrication of niobium-based oxides/oxynitrides/nitrides and their applications in dye-sensitized solar cells and anaerobic digestion

NASA Astrophysics Data System (ADS)

Zhang, Taihong; Yun, Sining; Li, Xue; Huang, Xinlei; Hou, Yuzhi; Liu, Yanfang; Li, Jing; Zhou, Xiao; Fang, Wen

2017-02-01

Transition metal compounds (TMCs), as a representative family of functional materials, have attracted great attention in the field of renewable energy. Herein, Nb3.49N4.56O0.44 and NbN are prepared from the nitridation of NbO2 in an NH3 atmosphere. These dual-functional Nb-based compounds were applied to dye-sensitized solar cells (DSSCs) and anaerobic digestion (AD), and the efficiency and stability of these DSSCs and AD systems were systematically evaluated. The Nb3.49N4.56O0.44 counter electrode (CE) exhibited considerable electrocatalytic activity and stability in I3- reduction in DSSCs, achieving photovoltaic performance comparable with Pt (6.36% vs. 7.19%). Furthermore, as accelerants, Nb-based compounds can greatly improve the AD environment, increasing substrate utilization and decreasing the hazards in the digestate. Compared with the control sample (409.2 mL/g·VS and 29.55%), substantially higher cumulative biogas production (437.1-522.7 mL/g·VS) and chemical oxygen demand removal rates (56.08%-65.19%) were achieved using Nb-based accelerants in the AD system. The nitridation technique is an effective and general means of converting Nb-based oxides into oxynitrides and nitrides. The Nb-based compounds with high electrocatalytic activities showed promise for DSSCs applications, while greatly enhancing the biodegradability of the AD system as accelerants. These findings could pave the way for multifunctional applications of TMCs in renewable energy fields.

Imaging correlates of pathology in corticobasal syndrome(Podcast)

PubMed Central

Whitwell, J.L.; Jack, C.R.; Boeve, B.F.; Parisi, J.E.; Ahlskog, J.E.; Drubach, D.A.; Senjem, M.L.; Knopman, D.S.; Petersen, R.C.; Dickson, D.W.; Josephs, K.A.

2010-01-01

Background: Corticobasal syndrome (CBS) can be associated with different underlying pathologies that are difficult to predict based on clinical presentation. The aim of this study was to determine whether patterns of atrophy on imaging could be useful to help predict underlying pathology in CBS. Methods: This was a case-control study of 24 patients with CBS who had undergone MRI during life and came to autopsy. Pathologic diagnoses included frontotemporal lobar degeneration (FTLD) with TDP-43 immunoreactivity in 5 (CBS-TDP), Alzheimer disease (AD) in 6 (CBS-AD), corticobasal degeneration in 7 (CBS-CBD), and progressive supranuclear palsy in 6 (CBS-PSP). Voxel-based morphometry and atlas-based parcellation were used to assess atrophy across the CBS groups and compared to 24 age- and gender-matched controls. Results: All CBS pathologic groups showed gray matter loss in premotor cortices, supplemental motor area, and insula on imaging. However, CBS-TDP and CBS-AD showed more widespread patterns of loss, with frontotemporal loss observed in CBS-TDP and temporoparietal loss observed in CBS-AD. CBS-TDP showed significantly greater loss in prefrontal cortex than the other groups, whereas CBS-AD showed significantly greater loss in parietal lobe than the other groups. The focus of loss was similar in CBS-CBD and CBS-PSP, although more severe in CBS-CBD. Conclusions: Imaging patterns of atrophy in CBS vary according to pathologic diagnosis. Widespread atrophy points toward a pathologic diagnosis of FTLD-TDP or AD, with frontotemporal loss suggesting FTLD-TDP and temporoparietal loss suggesting AD. On the contrary, more focal atrophy predominantly involving the premotor and supplemental motor area suggests CBD or PSP pathology. GLOSSARY AAL = automated anatomic labeling; AD = Alzheimer disease; CBD = corticobasal degeneration; CBS = corticobasal syndrome; CDR-SB = Clinical Dementia Rating sum of boxes; FDR = false discovery rate; FTLD = frontotemporal lobar degeneration; MMSE = Mini-Mental State Examination; PSP = progressive supranuclear palsy; ROI = region of interest; SMA = supplemental motor area; TDP = TDP-43 immunoreactivity; TIV = total intracranial volume; VBM = voxel-based morphometry. PMID:21098403

Beyond Test Scores: Adding Value to Assessment

ERIC Educational Resources Information Center

Rothman, Robert

2010-01-01

At a time when teacher quality has emerged as a key factor in student learning, a statistical technique that determines the "value added" that teachers bring to student achievement is getting new scrutiny. Value-added measures compare students' growth in achievement to their expected growth, based on prior achievement and demographic…

Robust Identification of Alzheimer's Disease subtypes based on cortical atrophy patterns.

PubMed

Park, Jong-Yun; Na, Han Kyu; Kim, Sungsoo; Kim, Hyunwook; Kim, Hee Jin; Seo, Sang Won; Na, Duk L; Han, Cheol E; Seong, Joon-Kyung

2017-03-09

Accumulating evidence suggests that Alzheimer's disease (AD) is heterogenous and can be classified into several subtypes. Here, we propose a robust subtyping method for AD based on cortical atrophy patterns and graph theory. We calculated similarities between subjects in their atrophy patterns throughout the whole brain, and clustered subjects with similar atrophy patterns using the Louvain method for modular organization extraction. We applied our method to AD patients recruited at Samsung Medical Center and externally validated our method by using the AD Neuroimaging Initiative (ADNI) dataset. Our method categorized very mild AD into three clinically distinct subtypes with high reproducibility (>90%); the parietal-predominant (P), medial temporal-predominant (MT), and diffuse (D) atrophy subtype. The P subtype showed the worst clinical presentation throughout the cognitive domains, while the MT and D subtypes exhibited relatively mild presentation. The MT subtype revealed more impaired language and executive function compared to the D subtype.

Robust Identification of Alzheimer’s Disease subtypes based on cortical atrophy patterns

NASA Astrophysics Data System (ADS)

Park, Jong-Yun; Na, Han Kyu; Kim, Sungsoo; Kim, Hyunwook; Kim, Hee Jin; Seo, Sang Won; Na, Duk L.; Han, Cheol E.; Seong, Joon-Kyung; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Liu, Enchi; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; Decarli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven G.; Shen, Li; Kelley, Faber; Kim, Sungeun; Nho, Kwangsik; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Doody, Rachelle S.; Villanueva Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; de Toledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; D'Agostino, Daniel, II; Kielb, Stephanie; Galvin, James E.; Pogorelec, Dana M.; Cerbone, Brittany; Michel, Christina A.; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; de Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Wong, Terence Z.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L.; Oakley, Maryann; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc Adams Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz Arrastia, Ramon; King, Richard; Weiner, Myron; Martin Cook, Kristen; Devous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H. S.; Lu, Po H.; Bartzokis, George; Graff Radford, Neill R.; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Farlow, Martin R.; Marie Hake, Ann; Matthews, Brandy R.; Herring, Scott; Hunt, Cynthia; van Dyck, Christopher H.; Carson, Richard E.; Macavoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging Yuek; Feldman, Howard; Mudge, Benita; Assaly, Michele; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Marsel Mesulam, Marek; Lipowski, Kristine; Kuo Wu, Chuang; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Lynn Johnson, Patricia; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Hudson, Leon; Fletcher, Evan; Carmichael, Owen; Olichney, John; Kittur, Smita; Borrie, Michael; Lee, T. Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Santulli, Robert B.; Kitzmiller, Tamar J.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabether; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Smith, Karen Elizabeth; Relkin, Norman; Chaing, Gloria; Raudin, Lisa; Smith, Amanda; Fargher, Kristin; Raj, Balebail Ashok

2017-03-01

Accumulating evidence suggests that Alzheimer’s disease (AD) is heterogenous and can be classified into several subtypes. Here, we propose a robust subtyping method for AD based on cortical atrophy patterns and graph theory. We calculated similarities between subjects in their atrophy patterns throughout the whole brain, and clustered subjects with similar atrophy patterns using the Louvain method for modular organization extraction. We applied our method to AD patients recruited at Samsung Medical Center and externally validated our method by using the AD Neuroimaging Initiative (ADNI) dataset. Our method categorized very mild AD into three clinically distinct subtypes with high reproducibility (>90%) the parietal-predominant (P), medial temporal-predominant (MT), and diffuse (D) atrophy subtype. The P subtype showed the worst clinical presentation throughout the cognitive domains, while the MT and D subtypes exhibited relatively mild presentation. The MT subtype revealed more impaired language and executive function compared to the D subtype.

Abnormal baseline brain activity in Alzheimer's disease patients with depression: a resting-state functional magnetic resonance imaging study.

PubMed

Liu, Xiaozheng; Guo, Zhongwei; Ding, Yanping; Li, Jiapeng; Wang, Gang; Hou, Hongtao; Chen, Xingli; Yu, Enyan

2017-07-01

As one of the most common mental disorders and the most important precursor of suicide in Alzheimer's disease (AD), depression is associated with a decline in both well-being and daily functioning. At present, the diagnosis of AD patients with depression (D-AD) is largely dependent on clinical signs and symptoms, and the precise neural correlate underlying D-AD is still not fully understood. The current study sought to investigate low-frequency oscillations at the voxel level in D-AD patients based on the amplitude of low-frequency fluctuations (ALFF) measured using resting-state functional magnetic resonance imaging. We examined 22 D-AD patients and 21 non-depressed AD (nD-AD) patients. The results revealed that D-AD patients exhibited increased ALFF values in the left caudate and thalamus and decreased ALFF values in the left middle temporal pole compared with nD-AD patients. These findings may provide further insight into the underlying neuropathophysiology of AD with depression.

A blood-based screening tool for Alzheimer's disease that spans serum and plasma: findings from TARC and ADNI.

PubMed

O'Bryant, Sid E; Xiao, Guanghua; Barber, Robert; Huebinger, Ryan; Wilhelmsen, Kirk; Edwards, Melissa; Graff-Radford, Neill; Doody, Rachelle; Diaz-Arrastia, Ramon

2011-01-01

There is no rapid and cost effective tool that can be implemented as a front-line screening tool for Alzheimer's disease (AD) at the population level. To generate and cross-validate a blood-based screener for AD that yields acceptable accuracy across both serum and plasma. Analysis of serum biomarker proteins were conducted on 197 Alzheimer's disease (AD) participants and 199 control participants from the Texas Alzheimer's Research Consortium (TARC) with further analysis conducted on plasma proteins from 112 AD and 52 control participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The full algorithm was derived from a biomarker risk score, clinical lab (glucose, triglycerides, total cholesterol, homocysteine), and demographic (age, gender, education, APOE*E4 status) data. Alzheimer's disease. 11 proteins met our criteria and were utilized for the biomarker risk score. The random forest (RF) biomarker risk score from the TARC serum samples (training set) yielded adequate accuracy in the ADNI plasma sample (training set) (AUC = 0.70, sensitivity (SN) = 0.54 and specificity (SP) = 0.78), which was below that obtained from ADNI cerebral spinal fluid (CSF) analyses (t-tau/Aβ ratio AUC = 0.92). However, the full algorithm yielded excellent accuracy (AUC = 0.88, SN = 0.75, and SP = 0.91). The likelihood ratio of having AD based on a positive test finding (LR+) = 7.03 (SE = 1.17; 95% CI = 4.49-14.47), the likelihood ratio of not having AD based on the algorithm (LR-) = 3.55 (SE = 1.15; 2.22-5.71), and the odds ratio of AD were calculated in the ADNI cohort (OR) = 28.70 (1.55; 95% CI = 11.86-69.47). It is possible to create a blood-based screening algorithm that works across both serum and plasma that provides a comparable screening accuracy to that obtained from CSF analyses.

Emergence of a new human adenovirus type 4 (Ad4) genotype: identification of a novel inverted terminal repeated (ITR) sequence from majority of Ad4 isolates from US military recruits.

PubMed

Houng, Huo-Shu H; Clavio, Sarah; Graham, Katherine; Kuschner, Robert; Sun, Wellington; Russell, Kevin L; Binn, Leonard N

2006-04-01

Ad4 is the principal etiological agent of acute respiratory disease (ARD) in the US military. Discovery of the novel 208bp inverted terminal repeated (ITR) sequence from a recent Ad4 Jax78 field isolate was totally distinct from the analogous 116bp ITR of Ad4 prototype. To investigate the origin and distribution of the novel Ad4 ITR sequence from ARD infections. Direct sequencing of ligated Ad ITR termini. The new Ad4 ITR was highly homologous with the ITRs of human Ad subgroup B. The left post-ITR region of Ad4 Jax78 was found to be highly homologous to the corresponding region of subgroup B Ads: 81% for Ad11 and 98% for Ad3 and Ad7. The right post-ITR region of Ad4 Jax78 contained a truncated classic ITR of the Ad4 prototype. The Ad4 Jax78 ITR most likely evolved from Ad4 prototype by substituting the Ad4 prototype ITR with the subgroup B Ads ITR. The ITR-based PCR assays developed from this study can be used to distinguish the new Ad4 genotype from the classical Ad4 prototype. The new Ad4 genotype was first detected in 1976 from Georgia, USA, and is the main causative agent of ARD infections in US military population.

Unravelling the active microbial community in a thermophilic anaerobic digester-microbial electrolysis cell coupled system under different conditions.

PubMed

Cerrillo, Míriam; Viñas, Marc; Bonmatí, August

2017-03-01

Thermophilic anaerobic digestion (AD) of pig slurry coupled to a microbial electrolysis cell (MEC) with a recirculation loop was studied at lab-scale as a strategy to increase AD stability when submitted to organic and nitrogen overloads. The system performance was studied, with the recirculation loop both connected and disconnected, in terms of AD methane production, chemical oxygen demand removal (COD) and volatile fatty acid (VFA) concentrations. Furthermore, the microbial population was quantitatively and qualitatively assessed through DNA and RNA-based qPCR and high throughput sequencing (MiSeq), respectively to identify the RNA-based active microbial populations from the total DNA-based microbial community composition both in the AD and MEC reactors under different operational conditions. Suppression of the recirculation loop reduced the AD COD removal efficiency (from 40% to 22%) and the methane production (from 0.32 to 0.03 m 3  m -3  d -1 ). Restoring the recirculation loop led to a methane production of 0.55 m 3  m -3  d -1 concomitant with maximum MEC COD and ammonium removal efficiencies of 29% and 34%, respectively. Regarding microbial analysis, the composition of the AD and MEC anode populations differed from really active microorganisms. Desulfuromonadaceae was revealed as the most active family in the MEC (18%-19% of the RNA relative abundance), while hydrogenotrophic methanogens (Methanobacteriaceae) dominated the AD biomass. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploring antismoking ads: appeals, themes, and consequences.

PubMed

Beaudoin, Christopher E

2002-01-01

In this study we seek a descriptive understanding of antismoking television advertising in light of the problem cigarette consumption poses for society today. We establish relationships between ad characteristics and whether ads have a youth or adult orientation, based on a content analysis of 197 antismoking television advertisements produced between 1991 and 1999. The study finds that youth-oriented ads have youth characters, sociability, and humor as common appeals, and social and short-term consequences. In contrast, adult-oriented ads relied on fear appeals and long-term, health-related consequences.

Free Chlorine and Cyanuric Acid Simulator Application ...

EPA Pesticide Factsheets

A web-based application designed to simulate the free chlorine in systems adding free chlorine and cyanuric acid, including the application of Dichlor and Trichlor. A web-based application designed to simulate the free chlorine in systems adding free chlorine and cyanuric acid, including the application of Dichlor and Trichlor.

Adding Insult to Imagery? Art Education and Censorship

ERIC Educational Resources Information Center

Sweeny, Robert W.

2007-01-01

The "Adding Insult to Imagery? Artistic Responses to Censorship and Mass-Media" exhibition opened in January 16, 2006, Kipp Gallery on the Indiana University of Pennsylvania campus. Eleven gallery-based works, 9 videos, and 10 web-based artworks comprised the show; each dealt with the relationship between censorship and mass mediated…

Individual subject classification for Alzheimer's disease based on incremental learning using a spatial frequency representation of cortical thickness data.

PubMed

Cho, Youngsang; Seong, Joon-Kyung; Jeong, Yong; Shin, Sung Yong

2012-02-01

Patterns of brain atrophy measured by magnetic resonance structural imaging have been utilized as significant biomarkers for diagnosis of Alzheimer's disease (AD). However, brain atrophy is variable across patients and is non-specific for AD in general. Thus, automatic methods for AD classification require a large number of structural data due to complex and variable patterns of brain atrophy. In this paper, we propose an incremental method for AD classification using cortical thickness data. We represent the cortical thickness data of a subject in terms of their spatial frequency components, employing the manifold harmonic transform. The basis functions for this transform are obtained from the eigenfunctions of the Laplace-Beltrami operator, which are dependent only on the geometry of a cortical surface but not on the cortical thickness defined on it. This facilitates individual subject classification based on incremental learning. In general, methods based on region-wise features poorly reflect the detailed spatial variation of cortical thickness, and those based on vertex-wise features are sensitive to noise. Adopting a vertex-wise cortical thickness representation, our method can still achieve robustness to noise by filtering out high frequency components of the cortical thickness data while reflecting their spatial variation. This compromise leads to high accuracy in AD classification. We utilized MR volumes provided by Alzheimer's Disease Neuroimaging Initiative (ADNI) to validate the performance of the method. Our method discriminated AD patients from Healthy Control (HC) subjects with 82% sensitivity and 93% specificity. It also discriminated Mild Cognitive Impairment (MCI) patients, who converted to AD within 18 months, from non-converted MCI subjects with 63% sensitivity and 76% specificity. Moreover, it showed that the entorhinal cortex was the most discriminative region for classification, which is consistent with previous pathological findings. In comparison with other classification methods, our method demonstrated high classification performance in both categories, which supports the discriminative power of our method in both AD diagnosis and AD prediction. Copyright © 2011 Elsevier Inc. All rights reserved.

Patterns of Energy Drink Advertising over U.S. Television Networks

PubMed Central

Emond, Jennifer A.; Sargent, James D.; Gilbert-Diamond, Diane

2014-01-01

Objective To describe programming themes and the inclusion of adolescents in the base audience for television channels with high levels of energy drink ad airtime. Design Secondary analysis of energy drink ad airtime over U.S. network and cable television channels (n=139) March 2012-February 2013. Programming themes and the inclusion of adolescents in each channel's base audience were extracted from cable television trade reports. Main Outcome Measure Energy drink ad airtime. Analysis Channels were ranked by airtime; programming themes and the inclusion of adolescents in the base audience were summarized for the 10 channels with the most airtime. Results Over the study year, 36,501 minutes (608 hours) were devoted to energy drink ads; the top 10 channels accounted 46.5% of such airtime. Programming themes for the top 10 channels were music (n=3), sports (n=3), action-adventure lifestyle (n=2), African-American lifestyle (n=1) and comedy (n=1). MTV2 ranked first in airtime devoted to energy drink ads. Six of the 10 channels with the most airtime included adolescents aged 12-17 years in their base audience. Conclusions and Implications Energy drink manufacturers primarily advertise on channels that likely appeal to adolescents. Nutritionists may wish to consider energy drink media literacy when advising adolescents about energy drink consumption. PMID:25754297

Synthesis and anticancer evaluation of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, 1,2,4-triazoles and Mannich bases.

PubMed

Megally Abdo, Nadia Youssef; Kamel, Mona Monir

2015-01-01

A series of 5-(pyridin-4-yl)-N-substituted-1,3,4-oxadiazol-2-amines (3a-d), 5-(pyridin-4-yl)-N-substituted-1,3,4-thiadiazol-2-amines (4a-d) and 5-(pyridin-4-yl)-4-substituted-1,2,4-triazole-3-thiones (5a-d) were obtained by the cyclization of hydrazinecarbothioamide derivatives 2a-d derived from isonicotinic acid hydrazide. Aminoalkylation of compounds 5a-d with formaldehyde and various secondary amines furnished the Mannich bases 6a-p. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses. All the compounds were screened for their in vitro anticancer activity against six human cancer cell lines and normal fibroblast cells. Sixteen of the tested compounds exhibited significant cytotoxicity against most cell lines. Among these derivatives, the Mannich bases 6j, 6m and 6p were found to exhibit the most potent activity. The Mannich base 6m showed more potent cytotoxic activity against gastric cancer NUGC (IC50=0.021 µM) than the standard CHS 828 (IC50=0.025 µM). Normal fibroblast cells WI38 were affected to a much lesser extent (IC50>10 µM).

Seroprevalence of Neutralizing Antibodies against Human Adenovirus Type-5 and Chimpanzee Adenovirus Type-68 in Cancer Patients

PubMed Central

Zhao, Hua; Xu, Can; Luo, Xiaoli; Wei, Feng; Wang, Ning; Shi, Huiying; Ren, Xiubao

2018-01-01

Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, P < 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, P = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, P < 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 (P < 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers against AdC68 with respect to AdHu5 in both healthy subjects and cancer subjects, especially in lung, laryngeal, esophageal, gastric, and cervical carcinomas. Also, the titer of NAbs against AdC68 was significantly lower than that against AdHu5 in the same clinical stage and age group (P < 0.05). Taken together, the present study showed that NAbs against AdC68 is much lower than AdHu5, especially in lung adenocarcinoma, laryngeal cancer, esophageal cancer, and cervical cancer patients. These results provided strong support for candidating AdC68 as a suitable vector of cancer vaccines. PMID:29563911

Modification to the Capsid of the Adenovirus Vector That Enhances Dendritic Cell Infection and Transgene-Specific Cellular Immune Responses

PubMed Central

Worgall, Stefan; Busch, Annette; Rivara, Michael; Bonnyay, David; Leopold, Philip L.; Merritt, Robert; Hackett, Neil R.; Rovelink, Peter W.; Bruder, Joseph T.; Wickham, Thomas J.; Kovesdi, Imi; Crystal, Ronald G.

2004-01-01

Adenovirus (Ad) gene transfer vectors can be used to transfer and express antigens and function as strong adjuvants and thus are useful platforms for the development of genetic vaccines. Based on the hypothesis that Ad vectors with enhanced infectibility of dendritic cells (DC) may be able to evoke enhanced immune responses against antigens encoded by the vector in vivo, the present study analyzes the vaccine potential of an Ad vector expressing β-galactosidase as a model antigen and genetically modified with RGD on the fiber knob [AdZ.F(RGD)] to more selectively infect DC and consequently enhance immunity against the β-galactosidase antigen. Infection of murine DC in vitro with AdZ.F(RGD) showed an eightfold-increased transgene expression following infection compared to AdZ (also expressing β-galactosidase, but with a wild-type capsid). Binding, cellular uptake, and trafficking in DC were also increased with AdZ.F(RGD) compared to AdZ. To determine whether AdZ.F(RGD) could evoke enhanced immune responses to β-galactosidase in vivo, C57BL/6 mice were immunized with AdZ.F(RGD) or AdZ subcutaneously via the footpad. Humoral responses with both vectors were comparable, with similar anti-β-galactosidase antibody levels following vector administration. However, cellular responses to β-galactosidase were significantly enhanced, with the frequency of CD4+ as well as the CD8+ β-galactosidase-specific gamma interferon response in cells isolated from the draining lymph nodes increased following immunization with AdZ.F(RGD) compared to Ad.Z (P < 0.01). Importantly, this enhanced cellular immune response of the AdZ.F(RGD) vector was sufficient to evoke enhanced inhibition of the growth of preexisting tumors expressing β-galactosidase: BALB/c mice implanted with the CT26 syngeneic β-galactosidase-expressing colon carcinoma cell line and subsequently immunized with AdZ.F(RGD) showed decreased tumor growth and improved survival compared to mice immunized with AdZ. These data demonstrate that addition of an RGD motif to the Ad fiber knob increases the infectibility of DC and leads to enhanced cellular immune responses to the Ad-transferred transgene, suggesting that the RGD capsid modification may be useful in developing Ad-based vaccines. PMID:14963160

Creation of Prototype Aircrew Protection Equipment Based on Face Anthropometry

DTIC Science & Technology

1993-12-01

AD-A273 865 AFIT/GSE/ENY/93D-2AD 27 86 DTIC ELECTE SDE.C 161993 A : CREATION OF PROTOTYPE AIRCREW PROTECTION EQUIPMENT BASED ON FACE ANTHROPOMETRY ...AIRCREW PROTECTION EQUIPMENT BASED ON FACE ANTHROPOMETRY THESIS Presented to the Faculty of the Graduate School of Engineering of the Air Force Institute...trans- form anthropomorphic surfaces into a prototype mask mold. xix CREATION OF PROTOTYPE AIRCREW PROTECTION EQUIPMENT BASED ON FACE ANTHROPOMETRY L

X-ray absorption fine structure analysis of molybdenum added to BaTiO3-based ceramics used for multilayer ceramic capacitors

NASA Astrophysics Data System (ADS)

Ogata, Yoichiro; Shimura, Tetsuo; Ryu, Minoru; Iwazaki, Yoshiki

2017-04-01

The effect of slight molybdenum doping of perovskite-type BaTiO3-based ceramics on the reliability of a multilayer ceramic capacitor (MLCC) and on the valence state of molybdenum in the BaTiO3-based ceramics has been investigated by highly accelerated lifetime tests and X-ray absorption fine structure analysis. The molybdenum added to the BaTiO3-based ceramics is located at Ti sites and improves the highly accelerated lifetime and lowers the initial dielectric resistivity in MLCCs. Through sintering in a reducing atmosphere, which is an important process in the fabrication of BaTiO3-based MLCCs, the oxidation state of the molybdenum added could be adjusted from +6 to a value close to +4.

Secure ADS-B authentication system and method

NASA Technical Reports Server (NTRS)

Viggiano, Marc J (Inventor); Valovage, Edward M (Inventor); Samuelson, Kenneth B (Inventor); Hall, Dana L (Inventor)

2010-01-01

A secure system for authenticating the identity of ADS-B systems, including: an authenticator, including a unique id generator and a transmitter transmitting the unique id to one or more ADS-B transmitters; one or more ADS-B transmitters, including a receiver receiving the unique id, one or more secure processing stages merging the unique id with the ADS-B transmitter's identification, data and secret key and generating a secure code identification and a transmitter transmitting a response containing the secure code and ADSB transmitter's data to the authenticator; the authenticator including means for independently determining each ADS-B transmitter's secret key, a receiver receiving each ADS-B transmitter's response, one or more secure processing stages merging the unique id, ADS-B transmitter's identification and data and generating a secure code, and comparison processing comparing the authenticator-generated secure code and the ADS-B transmitter-generated secure code and providing an authentication signal based on the comparison result.

Visual system manifestations of Alzheimer's disease.

PubMed

Kusne, Yael; Wolf, Andrew B; Townley, Kate; Conway, Mandi; Peyman, Gholam A

2017-12-01

Alzheimer's disease (AD) is an increasingly common disease with massive personal and economic costs. While it has long been known that AD impacts the visual system, there has recently been an increased focus on understanding both pathophysiological mechanisms that may be shared between the eye and brain and how related biomarkers could be useful for AD diagnosis. Here, were review pertinent cellular and molecular mechanisms of AD pathophysiology, the presence of AD pathology in the visual system, associated functional changes, and potential development of diagnostic tools based on the visual system. Additionally, we discuss links between AD and visual disorders, including possible pathophysiological mechanisms and their relevance for improving our understanding of AD. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

A Novel Virtual Reality-Based Training Protocol for the Enhancement of the “Mental Frame Syncing” in Individuals with Alzheimer's Disease: A Development-of-Concept Trial

PubMed Central

Serino, Silvia; Pedroli, Elisa; Tuena, Cosimo; De Leo, Gianluca; Stramba-Badiale, Marco; Goulene, Karine; Mariotti, Noemi G.; Riva, Giuseppe

2017-01-01

A growing body of evidence suggests that people with Alzheimer's Disease (AD) show compromised spatial abilities. In addition, there exists from the earliest stages of AD a specific impairment in “mental frame syncing,” which is the ability to synchronize an allocentric viewpoint-independent representation (including object-to-object information) with an egocentric one by computing the bearing of each relevant “object” in the environment in relation to the stored heading in space (i.e., information about our viewpoint contained in the allocentric viewpoint-dependent representation). The main objective of this development-of-concept trial was to evaluate the efficacy of a novel VR-based training protocol focused on the enhancement of the “mental frame syncing” of the different spatial representations in subjects with AD. We recruited 20 individuals with AD who were randomly assigned to either “VR-based training” or “Control Group.” Moreover, eight cognitively healthy elderly individuals were recruited to participate in the VR-based training in order to have a different comparison group. Based on a neuropsychological assessment, our results indicated a significant improvement in long-term spatial memory after the VR-based training for patients with AD; this means that transference of improvements from the VR-based training to more general aspects of spatial cognition was observed. Interestingly, there was also a significant effect of VR-based training on executive functioning for cognitively healthy elderly individuals. In sum, VR could be considered as an advanced embodied tool suitable for treating spatial recall impairments. PMID:28798682

Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score

PubMed Central

Cupples, L. Adrienne; Thompson, Wesley K.; Besser, Lilah; Kukull, Walter A.; Holland, Dominic; Chen, Chi-Hua; Brewer, James B.; Karow, David S.; Kauppi, Karolina; Bonham, Luke W.; Rosen, Howard J.; Miller, Bruce L.; Dillon, William P.; Wilson, David M.; Pericak-Vance, Margaret; Haines, Jonathan L.; Farrer, Lindsay A.; Mayeux, Richard; Hardy, John; Goate, Alison M.; Schellenberg, Gerard D.; Andreassen, Ole A.

2017-01-01

Background Identifying individuals at risk for developing Alzheimer disease (AD) is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, genetic information has not been integrated into an epidemiological framework for risk prediction. Methods and findings Using genotype data from 17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer’s Project (IGAP Stage 1), we identified AD-associated SNPs (at p < 10−5). We then integrated these AD-associated SNPs into a Cox proportional hazard model using genotype data from a subset of 6,409 AD patients and 9,386 older controls from Phase 1 of the Alzheimer’s Disease Genetics Consortium (ADGC), providing a polygenic hazard score (PHS) for each participant. By combining population-based incidence rates and the genotype-derived PHS for each individual, we derived estimates of instantaneous risk for developing AD, based on genotype and age, and tested replication in multiple independent cohorts (ADGC Phase 2, National Institute on Aging Alzheimer’s Disease Center [NIA ADC], and Alzheimer’s Disease Neuroimaging Initiative [ADNI], total n = 20,680). Within the ADGC Phase 1 cohort, individuals in the highest PHS quartile developed AD at a considerably lower age and had the highest yearly AD incidence rate. Among APOE ε3/3 individuals, the PHS modified expected age of AD onset by more than 10 y between the lowest and highest deciles (hazard ratio 3.34, 95% CI 2.62–4.24, p = 1.0 × 10−22). In independent cohorts, the PHS strongly predicted empirical age of AD onset (ADGC Phase 2, r = 0.90, p = 1.1 × 10−26) and longitudinal progression from normal aging to AD (NIA ADC, Cochran–Armitage trend test, p = 1.5 × 10−10), and was associated with neuropathology (NIA ADC, Braak stage of neurofibrillary tangles, p = 3.9 × 10−6, and Consortium to Establish a Registry for Alzheimer’s Disease score for neuritic plaques, p = 6.8 × 10−6) and in vivo markers of AD neurodegeneration (ADNI, volume loss within the entorhinal cortex, p = 6.3 × 10−6, and hippocampus, p = 7.9 × 10−5). Additional prospective validation of these results in non-US, non-white, and prospective community-based cohorts is necessary before clinical use. Conclusions We have developed a PHS for quantifying individual differences in age-specific genetic risk for AD. Within the cohorts studied here, polygenic architecture plays an important role in modifying AD risk beyond APOE. With thorough validation, quantification of inherited genetic variation may prove useful for stratifying AD risk and as an enrichment strategy in therapeutic trials. PMID:28323831

Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score.

PubMed

Desikan, Rahul S; Fan, Chun Chieh; Wang, Yunpeng; Schork, Andrew J; Cabral, Howard J; Cupples, L Adrienne; Thompson, Wesley K; Besser, Lilah; Kukull, Walter A; Holland, Dominic; Chen, Chi-Hua; Brewer, James B; Karow, David S; Kauppi, Karolina; Witoelar, Aree; Karch, Celeste M; Bonham, Luke W; Yokoyama, Jennifer S; Rosen, Howard J; Miller, Bruce L; Dillon, William P; Wilson, David M; Hess, Christopher P; Pericak-Vance, Margaret; Haines, Jonathan L; Farrer, Lindsay A; Mayeux, Richard; Hardy, John; Goate, Alison M; Hyman, Bradley T; Schellenberg, Gerard D; McEvoy, Linda K; Andreassen, Ole A; Dale, Anders M

2017-03-01

Identifying individuals at risk for developing Alzheimer disease (AD) is of utmost importance. Although genetic studies have identified AD-associated SNPs in APOE and other genes, genetic information has not been integrated into an epidemiological framework for risk prediction. Using genotype data from 17,008 AD cases and 37,154 controls from the International Genomics of Alzheimer's Project (IGAP Stage 1), we identified AD-associated SNPs (at p < 10-5). We then integrated these AD-associated SNPs into a Cox proportional hazard model using genotype data from a subset of 6,409 AD patients and 9,386 older controls from Phase 1 of the Alzheimer's Disease Genetics Consortium (ADGC), providing a polygenic hazard score (PHS) for each participant. By combining population-based incidence rates and the genotype-derived PHS for each individual, we derived estimates of instantaneous risk for developing AD, based on genotype and age, and tested replication in multiple independent cohorts (ADGC Phase 2, National Institute on Aging Alzheimer's Disease Center [NIA ADC], and Alzheimer's Disease Neuroimaging Initiative [ADNI], total n = 20,680). Within the ADGC Phase 1 cohort, individuals in the highest PHS quartile developed AD at a considerably lower age and had the highest yearly AD incidence rate. Among APOE ε3/3 individuals, the PHS modified expected age of AD onset by more than 10 y between the lowest and highest deciles (hazard ratio 3.34, 95% CI 2.62-4.24, p = 1.0 × 10-22). In independent cohorts, the PHS strongly predicted empirical age of AD onset (ADGC Phase 2, r = 0.90, p = 1.1 × 10-26) and longitudinal progression from normal aging to AD (NIA ADC, Cochran-Armitage trend test, p = 1.5 × 10-10), and was associated with neuropathology (NIA ADC, Braak stage of neurofibrillary tangles, p = 3.9 × 10-6, and Consortium to Establish a Registry for Alzheimer's Disease score for neuritic plaques, p = 6.8 × 10-6) and in vivo markers of AD neurodegeneration (ADNI, volume loss within the entorhinal cortex, p = 6.3 × 10-6, and hippocampus, p = 7.9 × 10-5). Additional prospective validation of these results in non-US, non-white, and prospective community-based cohorts is necessary before clinical use. We have developed a PHS for quantifying individual differences in age-specific genetic risk for AD. Within the cohorts studied here, polygenic architecture plays an important role in modifying AD risk beyond APOE. With thorough validation, quantification of inherited genetic variation may prove useful for stratifying AD risk and as an enrichment strategy in therapeutic trials.

Ligand-functionalized degradable polyplexes formed by cationic poly(aspartic acid)-grafted chitosan-cyclodextrin conjugates

NASA Astrophysics Data System (ADS)

Song, Hai-Qing; Li, Rui-Quan; Duan, Shun; Yu, Bingran; Zhao, Hong; Chen, Da-Fu; Xu, Fu-Jian

2015-03-01

Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE-FA/pDNA, and ternary CCPE-FA/CCPE/pDNA (prepared by layer-by-layer assembly) polyplexes were investigated in detail using different cell lines. The CCPE-based polyplexes displayed much higher transfection efficiencies than the CS-based polyplexes reported earlier by us. The ternary polyplexes of CCPE-FA/CCPE/pDNA produced excellent gene transfection abilities in the folate receptor (FR)-positive tumor cells. This work would provide a promising means to produce highly efficient polyplexes for future gene therapy applications.Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE-FA/pDNA, and ternary CCPE-FA/CCPE/pDNA (prepared by layer-by-layer assembly) polyplexes were investigated in detail using different cell lines. The CCPE-based polyplexes displayed much higher transfection efficiencies than the CS-based polyplexes reported earlier by us. The ternary polyplexes of CCPE-FA/CCPE/pDNA produced excellent gene transfection abilities in the folate receptor (FR)-positive tumor cells. This work would provide a promising means to produce highly efficient polyplexes for future gene therapy applications. Electronic supplementary information (ESI) available: 1H NMR assay, synthetic route of Ad-FA, AFM images and cellular internalization rate can be found in ESI. See DOI: 10.1039/c4nr07515c

Risk of hip fracture in Addison's disease: a population-based cohort study.

PubMed

Björnsdottir, S; Sääf, M; Bensing, S; Kämpe, O; Michaëlsson, K; Ludvigsson, J F

2011-08-01

The results of studies of bone mineral density in Addison's disease (AD) are inconsistent. There are no published data on hip fracture risk in patients with AD. In this study, we compare hip fracture risk in adults with and without AD. A population-based cohort study. Through the Swedish National Patient Register and the Total Population Register, we identified 3219 patients without prior hip fracture who were diagnosed with AD at the age of ≥30 years during the period 1964-2006 and 31 557 age- and sex-matched controls. Time to hip fracture was measured. We observed 221 hip fractures (6.9%) in patients with AD and 846 (2.7%) in the controls. Patients with AD had a higher risk of hip fracture [hazard ratio (HR) = 1.8; 95% confidence interval (CI), 1.6-2.1; P < 0.001]. This risk increase was independent of sex and age at or calendar period of diagnosis. Risk estimates did not change with adjustment for type 1 diabetes, autoimmune thyroid disease, rheumatoid arthritis or coeliac disease. Women diagnosed with AD ≤50 years old had the highest risk of hip fracture (HR = 2.7; 95 % CI, 1.6-4.5). We found a positive association between hip fracture and undiagnosed AD [odds ratio (OR) = 2.4; 95 % CI, 2.1-3.0] with the highest risk estimates in the last year before AD diagnosis (OR = 2.8; 95 % CI, 1.8-4.2). Both clinically undiagnosed and diagnosed AD was associated with hip fractures, with the highest relative risk seen in women diagnosed with AD ≤50 years of age. © 2011 The Association for the Publication of the Journal of Internal Medicine.

Game-based combined cognitive and neurofeedback training using Focus Pocus reduces symptom severity in children with diagnosed AD/HD and subclinical AD/HD.

PubMed

Johnstone, Stuart J; Roodenrys, Steven J; Johnson, Kirsten; Bonfield, Rebecca; Bennett, Susan J

2017-06-01

Previous studies report reductions in symptom severity after combined working memory (WM) and inhibitory control (IC) training in children with AD/HD. Based on theoretical accounts of the role of arousal/attention modulation problems in AD/HD, the current study examined the efficacy of combined WM, IC, and neurofeedback training in children with AD/HD and subclinical AD/HD. Using a randomized waitlist control design, 85 children were randomly allocated to a training or waitlist condition and completed pre- and post-training assessments of overt behavior, trained and untrained cognitive task performance, and resting and task-related EEG activity. The training group completed twenty-five sessions of training using Focus Pocus software at home over a 7 to 8-week period. Trainees improved at the trained tasks, while enjoyment and engagement declined across sessions. After training, AD/HD symptom severity was reduced in the AD/HD and subclinical groups according to parents, and in the former group only according to blinded teachers and significant-others. There were minor improvements in two of six near-transfer tasks, and evidence of far-transfer of training effects in four of five far-transfer tasks. Frontal region changes indicated normalization of atypical EEG features with reduced delta and increased alpha activity. It is concluded that technology developments provide an interesting a vehicle for delivering interventions and that, while further research is needed, combined WM, IC, and neurofeedback training can reduce AD/HD symptom severity in children with AD/HD and may also be beneficial to children with subclinical AD/HD. Copyright © 2017 Elsevier B.V. All rights reserved.

Automatic voxel-based morphometry of structural MRI by SPM8 plus diffeomorphic anatomic registration through exponentiated lie algebra improves the diagnosis of probable Alzheimer Disease.

PubMed

Matsuda, H; Mizumura, S; Nemoto, K; Yamashita, F; Imabayashi, E; Sato, N; Asada, T

2012-06-01

The necessity for structural MRI is greater than ever to both diagnose AD in its early stage and objectively evaluate its progression. We propose a new VBM-based software program for automatic detection of early specific atrophy in AD. A target VOI was determined by group comparison of 30 patients with very mild AD and 40 age-matched healthy controls by using SPM. Then this target VOI was incorporated into a newly developed automated software program independently running on a Windows PC for VBM by using SPM8 plus DARTEL. ROC analysis was performed for discrimination of 116 other patients with AD with very mild stage (n = 45), mild stage (n = 30) and moderate-to-advanced stages (n = 41) from 40 other age-matched healthy controls by using a z score map in the target VOI. Medial temporal structures involving the entire region of the entorhinal cortex, hippocampus, and amygdala showed significant atrophy in the patients with very mild AD and were determined as a target VOI. When we used the severity score of atrophy in this target VOI, 91.6%, 95.8%, and 98.2% accuracies were obtained in the very mild AD, mild AD, and moderate-to-severe AD groups, respectively. In the very mild AD group, a high specificity of 97.5% with a sensitivity of 86.4% was obtained, and age at onset of AD did not influence this accuracy. This software program with application of SPM8 plus DARTEL to VBM provides a high performance for AD diagnosis by using MRI.

Early detection of Alzheimer disease: methods, markers, and misgivings.

PubMed

Green, R C; Clarke, V C; Thompson, N J; Woodard, J L; Letz, R

1997-01-01

There is at present no reliable predictive test for most forms of Alzheimer disease (AD). Although some information about future risk for disease is available in theory through ApoE genotyping, it is of limited accuracy and utility. Once neuroprotective treatments are available for AD, reliable early detection will become a key component of the treatment strategy. We recently conducted a pilot survey eliciting attitudes and beliefs toward an unspecified and hypothetical predictive test for AD. The survey was completed by a convenience sample of 176 individuals, aged 22-77, which was 75% female, 30% African-American, and of which 33% had a family member with AD. The survey revealed that 69% of this sample would elect to obtain predictive testing for AD if the test were 100% accurate. Individuals were more likely to desire predictive testing if they had an a priori belief that they would develop AD (p = 0.0001), had a lower educational level (p = 0.003), were worried that they would develop AD (p = 0.02), had a self-defined history of depression (p = 0.04), and had a family member with AD (p = 0.04). However, the desire for predictive testing was not significantly associated with age, gender, ethnicity, or income. The desire to obtain predictive testing for AD decreased as the assumed accuracy of the hypothetical test decreased. A better short-term strategy for early detection of AD may be computer-based neuropsychological screening of at-risk (older aged) individuals to identify very early cognitive impairment. Individuals identified in this manner could be referred for diagnostic evaluation and early cases of AD could be identified and treated. A new self-administered, touch-screen, computer-based, neuropsychological screening instrument called Neurobehavioral Evaluation System-3 is described, which may facilitate this type of screening.

The Reliability, Impact, and Cost-Effectiveness of Value-Added Teacher Assessment Methods

ERIC Educational Resources Information Center

Yeh, Stuart S.

2012-01-01

This article reviews evidence regarding the intertemporal reliability of teacher rankings based on value-added methods. Value-added methods exhibit low reliability, yet are broadly supported by prominent educational researchers and are increasingly being used to evaluate and fire teachers. The article then presents a cost-effectiveness analysis…

Sensitivity of Teacher Value-Added Estimates to Student and Peer Control Variables

ERIC Educational Resources Information Center

Johnson, Matthew T.; Lipscomb, Stephen; Gill, Brian

2015-01-01

Teacher value-added models (VAMs) must isolate teachers' contributions to student achievement to be valid. Well-known VAMs use different specifications, however, leaving policymakers with little clear guidance for constructing a valid model. We examine the sensitivity of teacher value-added estimates under different models based on whether they…

Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D.

PubMed

Abbink, Peter; Lemckert, Angelique A C; Ewald, Bonnie A; Lynch, Diana M; Denholtz, Matthew; Smits, Shirley; Holterman, Lennart; Damen, Irma; Vogels, Ronald; Thorner, Anna R; O'Brien, Kara L; Carville, Angela; Mansfield, Keith G; Goudsmit, Jaap; Havenga, Menzo J E; Barouch, Dan H

2007-05-01

Recombinant adenovirus serotype 5 (rAd5) vector-based vaccines are currently being developed for both human immunodeficiency virus type 1 and other pathogens. The potential limitations associated with rAd5 vectors, however, have led to the construction of novel rAd vectors derived from rare Ad serotypes. Several rare serotype rAd vectors have already been described, but a detailed comparison of multiple rAd vectors from subgroups B and D has not previously been reported. Such a comparison is critical for selecting optimal rAd vectors for advancement into clinical trials. Here we describe the construction of three novel rAd vector systems from Ad26, Ad48, and Ad50. We report comparative seroprevalence and immunogenicity studies involving rAd11, rAd35, and rAd50 vectors from subgroup B; rAd26, rAd48, and rAd49 vectors from subgroup D; and rAd5 vectors from subgroup C. All six rAd vectors from subgroups B and D exhibited low seroprevalence in a cohort of 200 individuals from sub-Saharan Africa, and they elicited Gag-specific cellular immune responses in mice both with and without preexisting anti-Ad5 immunity. The rAd vectors from subgroup D were also evaluated using rhesus monkeys and were shown to be immunogenic after a single injection. The rAd26 vectors proved the most immunogenic among the rare serotype rAd vectors studied, although all rare serotype rAd vectors were still less potent than rAd5 vectors in the absence of anti-Ad5 immunity. These studies substantially expand the portfolio of rare serotype rAd vectors that may prove useful as vaccine vectors for the developing world.

Dextran and gelatin based photocrosslinkable tissue adhesive.

PubMed

Wang, Tao; Nie, Jun; Yang, Dongzhi

2012-11-06

A two-component tissue adhesive based on biocompatible and bio-degradable polymers (oxidized urethane dextran (Dex-U-AD) and gelatin) was prepared and photocrosslinked under the ultraviolet (UV) irradiation. The adhesive could adhere to surface of gelatin, which simulated the human tissue steadily. The structures of above Dex-U-AD were characterized by FTIR, (1)H NMR spectroscopy and XRD. The adhesion property of result products was evaluated by lap-shear test. The maximum adhesion strength could reach to 4.16±0.72 MPa which was significantly higher than that of fibrin glue. The photopolymerization process of Dex-U-AD/gelatin was monitored by real time infrared spectroscopy (RTIR). It took less than 5 min to complete the curing process. The cytotoxicity of Dex-U-AD/gelatin also was evaluated which indicated that Dex-U-AD/gelatin gels were nontoxic to L929 cell. The relationship between all the above-mentioned properties and degree of oxidization of Dex-U-AD was assessed. The obtained products have the potential to serve as tissue adhesive in the future. Copyright © 2012 Elsevier Ltd. All rights reserved.

Correlating brain blood oxygenation level dependent (BOLD) fractal dimension mapping with magnetic resonance spectroscopy (MRS) in Alzheimer's disease.

PubMed

Warsi, Mohammed A; Molloy, William; Noseworthy, Michael D

2012-10-01

To correlate temporal fractal structure of resting state blood oxygen level dependent (rsBOLD) functional magnetic resonance imaging (fMRI) with in vivo proton magnetic resonance spectroscopy ((1)H-MRS), in Alzheimer's disease (AD) and healthy age-matched normal controls (NC). High temporal resolution (4 Hz) rsBOLD signal and single voxel (left putamen) magnetic resonance spectroscopy data was acquired in 33 AD patients and 13 NC. The rsBOLD data was analyzed using two types of fractal dimension (FD) analysis based on relative dispersion and frequency power spectrum. Comparisons in FD were performed between AD and NC, and FD measures were correlated with (1)H-MRS findings. Temporal fractal analysis of rsBOLD, was able to differentiate AD from NC subjects (P = 0.03). Low FD correlated with markers of AD severity including decreased concentrations of N-acetyl aspartate (R = 0.44, P = 0.015) and increased myoinositol (mI) (R = -0.45, P = 0.012). Based on these results we suggest fractal analysis of rsBOLD could provide an early marker of AD.

The cost of Alzheimer's disease in China and re-estimation of costs worldwide.

PubMed

Jia, Jianping; Wei, Cuibai; Chen, Shuoqi; Li, Fangyu; Tang, Yi; Qin, Wei; Zhao, Lina; Jin, Hongmei; Xu, Hui; Wang, Fen; Zhou, Aihong; Zuo, Xiumei; Wu, Liyong; Han, Ying; Han, Yue; Huang, Liyuan; Wang, Qi; Li, Dan; Chu, Changbiao; Shi, Lu; Gong, Min; Du, Yifeng; Zhang, Jiewen; Zhang, Junjian; Zhou, Chunkui; Lv, Jihui; Lv, Yang; Xie, Haiqun; Ji, Yong; Li, Fang; Yu, Enyan; Luo, Benyan; Wang, Yanjiang; Yang, Shanshan; Qu, Qiumin; Guo, Qihao; Liang, Furu; Zhang, Jintao; Tan, Lan; Shen, Lu; Zhang, Kunnan; Zhang, Jinbiao; Peng, Dantao; Tang, Muni; Lv, Peiyuan; Fang, Boyan; Chu, Lan; Jia, Longfei; Gauthier, Serge

2018-04-01

The socioeconomic costs of Alzheimer's disease (AD) in China and its impact on global economic burden remain uncertain. We collected data from 3098 patients with AD in 81 representative centers across China and estimated AD costs for individual patient and total patients in China in 2015. Based on this data, we re-estimated the worldwide costs of AD. The annual socioeconomic cost per patient was US $19,144.36, and total costs were US $167.74 billion in 2015. The annual total costs are predicted to reach US $507.49 billion in 2030 and US $1.89 trillion in 2050. Based on our results, the global estimates of costs for dementia were US $957.56 billion in 2015, and will be US $2.54 trillion in 2030, and US $9.12 trillion in 2050, much more than the predictions by the World Alzheimer Report 2015. China bears a heavy burden of AD costs, which greatly change the estimates of AD cost worldwide. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Curcumin-I Knoevenagel's condensates and their Schiff's bases as anticancer agents: synthesis, pharmacological and simulation studies.

PubMed

Ali, Imran; Haque, Ashanul; Saleem, Kishwar; Hsieh, Ming Fa

2013-07-01

Pyrazolealdehydes (4a-d), Knoevenagel's condensates (5a-d) and Schiff's bases (6a-d) of curcumin-I were synthesized, purified and characterized. Hemolysis assays, cell line activities, DNA bindings and docking studies were carried out. These compounds were lesser hemolytic than standard drug doxorubicin. Minimum cell viability (MCF-7; wild) observed was 59% (1.0 μg/mL) whereas the DNA binding constants ranged from 1.4×10(3) to 8.1×10(5) M(-1). The docking energies varied from -7.30 to -13.4 kcal/mol. It has been observed that DNA-compound adducts were stabilized by three governing forces (Van der Wall's, H-bonding and electrostatic attractions). It has also been observed that compounds 4a-d preferred to enter minor groove while 5a-d and 6a-d interacted with major grooves of DNA. The anticancer activities of the reported compounds might be due to their interactions with DNA. These results indicated the bright future of the reported compounds as anticancer agents. Copyright © 2013 Elsevier Ltd. All rights reserved.

Improved multimodal biomarkers for Alzheimer's disease and mild cognitive impairment diagnosis: data from ADNI

NASA Astrophysics Data System (ADS)

Martinez-Torteya, Antonio; Treviño-Alvarado, Víctor; Tamez-Peña, José

2013-02-01

The accurate diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) confers many clinical research and patient care benefits. Studies have shown that multimodal biomarkers provide better diagnosis accuracy of AD and MCI than unimodal biomarkers, but their construction has been based on traditional statistical approaches. The objective of this work was the creation of accurate AD and MCI diagnostic multimodal biomarkers using advanced bioinformatics tools. The biomarkers were created by exploring multimodal combinations of features using machine learning techniques. Data was obtained from the ADNI database. The baseline information (e.g. MRI analyses, PET analyses and laboratory essays) from AD, MCI and healthy control (HC) subjects with available diagnosis up to June 2012 was mined for case/controls candidates. The data mining yielded 47 HC, 83 MCI and 43 AD subjects for biomarker creation. Each subject was characterized by at least 980 ADNI features. A genetic algorithm feature selection strategy was used to obtain compact and accurate cross-validated nearest centroid biomarkers. The biomarkers achieved training classification accuracies of 0.983, 0.871 and 0.917 for HC vs. AD, HC vs. MCI and MCI vs. AD respectively. The constructed biomarkers were relatively compact: from 5 to 11 features. Those multimodal biomarkers included several widely accepted univariate biomarkers and novel image and biochemical features. Multimodal biomarkers constructed from previously and non-previously AD associated features showed improved diagnostic performance when compared to those based solely on previously AD associated features.

Integrated Display and Simulation for Automatic Dependent Surveillance–Broadcast and Traffic Collision Avoidance System Data Fusion

PubMed Central

Wang, Yanran; Xiao, Gang; Dai, Zhouyun

2017-01-01

Automatic Dependent Surveillance–Broadcast (ADS-B) is the direction of airspace surveillance development. Research analyzing the benefits of Traffic Collision Avoidance System (TCAS) and ADS-B data fusion is almost absent. The paper proposes an ADS-B minimum system from ADS-B In and ADS-B Out. In ADS-B In, a fusion model with a variable sampling Variational Bayesian-Interacting Multiple Model (VSVB-IMM) algorithm is proposed for integrated display and an airspace traffic situation display is developed by using ADS-B information. ADS-B Out includes ADS-B Out transmission based on a simulator platform and an Unmanned Aerial Vehicle (UAV) platform. This paper describes the overall implementation of ADS-B minimum system, including theoretical model design, experimental simulation verification, engineering implementation, results analysis, etc. Simulation and implementation results show that the fused system has better performance than each independent subsystem and it can work well in engineering applications. PMID:29137194

Adenoviral Vector Immunity: Its Implications and circumvention strategies

PubMed Central

Ahi, Yadvinder S.; Bangari, Dinesh S.; Mittal, Suresh K.

2014-01-01

Adenoviral (Ad) vectors have emerged as a promising gene delivery platform for a variety of therapeutic and vaccine purposes during last two decades. However, the presence of preexisting Ad immunity and the rapid development of Ad vector immunity still pose significant challenges to the clinical use of these vectors. Innate inflammatory response following Ad vector administration may lead to systemic toxicity, drastically limit vector transduction efficiency and significantly abbreviate the duration of transgene expression. Currently, a number of approaches are being extensively pursued to overcome these drawbacks by strategies that target either the host or the Ad vector. In addition, significant progress has been made in the development of novel Ad vectors based on less prevalent human Ad serotypes and nonhuman Ad. This review provides an update on our current understanding of immune responses to Ad vectors and delineates various approaches for eluding Ad vector immunity. Approaches targeting the host and those targeting the vector are discussed in light of their promises and limitations. PMID:21453277

Automated diagnosis of Alzheimer's disease with multi-atlas based whole brain segmentations

NASA Astrophysics Data System (ADS)

Luo, Yuan; Tang, Xiaoying

2017-03-01

Voxel-based analysis is widely used in quantitative analysis of structural brain magnetic resonance imaging (MRI) and automated disease detection, such as Alzheimer's disease (AD). However, noise at the voxel level may cause low sensitivity to AD-induced structural abnormalities. This can be addressed with the use of a whole brain structural segmentation approach which greatly reduces the dimension of features (the number of voxels). In this paper, we propose an automatic AD diagnosis system that combines such whole brain segmen- tations with advanced machine learning methods. We used a multi-atlas segmentation technique to parcellate T1-weighted images into 54 distinct brain regions and extract their structural volumes to serve as the features for principal-component-analysis-based dimension reduction and support-vector-machine-based classification. The relationship between the number of retained principal components (PCs) and the diagnosis accuracy was systematically evaluated, in a leave-one-out fashion, based on 28 AD subjects and 23 age-matched healthy subjects. Our approach yielded pretty good classification results with 96.08% overall accuracy being achieved using the three foremost PCs. In addition, our approach yielded 96.43% specificity, 100% sensitivity, and 0.9891 area under the receiver operating characteristic curve.

Functional Neuroanatomical Correlates of The Frontal Assessment Battery Performance in Alzheimer Disease: A FDG-PET Study.

PubMed

Lee, Jun Ho; Byun, Min Soo; Sohn, Bo Kyung; Choe, Young Min; Yi, Dahyun; Han, Ji Young; Choi, Hyo Jung; Baek, Hyewon; Woo, Jong Inn; Lee, Dong Young

2015-09-01

We aimed to elucidate the functional neuroanatomical correlates of Frontal Assessment Battery (FAB) performances by applying [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to a large population of patients with Alzheimer disease (AD). The FAB was administered to 177 patients with AD, and regional cerebral glucose metabolism (rCMglc) was measured by FDG-PET scan. Correlations between FAB scores and rCMglc were explored using both region-of-interest-based (ROI-based) and voxel-based approaches. The ROI-based analysis showed that FAB scores correlated with the rCMglc of the dorsolateral prefrontal cortices. Voxel-based approach revealed significant positive correlations between FAB scores and rCMglc which were in various cortical regions including the temporal and parietal cortices as well as frontal regions, independent of age, gender, and education. After controlling the effect of global disease severity with Mini-Mental State Examination score, significant positive correlation was found only in the bilateral prefrontal regions. Although FAB scores are influenced by temporoparietal dysfunction due to the overall progression of AD, it likely reflects prefrontal dysfunction specifically regardless of global cognitive state or disease severity in patients with AD. © The Author(s) 2015.

A prime-boost immunization regimen based on a simian adenovirus 36 vectored multi-stage malaria vaccine induces protective immunity in mice.

PubMed

Fonseca, Jairo A; McCaffery, Jessica N; Kashentseva, Elena; Singh, Balwan; Dmitriev, Igor P; Curiel, David T; Moreno, Alberto

2017-05-31

Malaria remains a considerable burden on public health. In 2015, the WHO estimates there were 212 million malaria cases causing nearly 429,000 deaths globally. A highly effective malaria vaccine is needed to reduce the burden of this disease. We have developed an experimental vaccine candidate (PyCMP) based on pre-erythrocytic (CSP) and erythrocytic (MSP1) stage antigens derived from the rodent malaria parasite P. yoelii. Our protein-based vaccine construct induces protective antibodies and CD4 + T cell responses. Based on evidence that viral vectors increase CD8 + T cell-mediated immunity, we also have tested heterologous prime-boost immunization regimens that included human adenovirus serotype 5 vector (Ad5), obtaining protective CD8 + T cell responses. While Ad5 is commonly used for vaccine studies, the high prevalence of pre-existing immunity to Ad5 severely compromises its utility. Here, we report the use of the novel simian adenovirus 36 (SAd36) as a candidate for a vectored malaria vaccine since this virus is not known to infect humans, and it is not neutralized by anti-Ad5 antibodies. Our study shows that the recombinant SAd36PyCMP can enhance specific CD8 + T cell response and elicit similar antibody titers when compared to an immunization regimen including the recombinant Ad5PyCMP. The robust immune responses induced by SAd36PyCMP are translated into a lower parasite load following P. yoelii infectious challenge when compared to mice immunized with Ad5PyCMP. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dementia Research: Populations, Progress, Problems, and Predictions.

PubMed

Hunter, Sally; Smailagic, Nadja; Brayne, Carol

2018-05-16

Alzheimer's disease (AD) is a clinicopathologically defined syndrome leading to cognitive impairment. Following the recent failures of amyloid-based randomized controlled trials to change the course of AD, there are growing calls for a re-evaluation of basic AD research. Epidemiology offers one approach to integrating the available evidence. Here we examine relationships between evidence from population-based, clinicopathological studies of brain aging and a range of hypotheses from all areas of AD research. We identify various problems, including a lack of systematic approach to measurement of clinical and neuropathological factors associated with dementia in experimental and clinical settings, poor understanding of the strengths and weaknesses of different observational and experimental designs, a lack of clarity in relation to disease definitions from the clinical, neuropathological, and molecular perspectives, inadequate characterization of brain aging in the human population, difficulties in translation between laboratory-based and population-based evidence bases, and a lack of communication between different sections of the dementia research community. Population studies highlight complexity and predict that therapeutic approaches based on single disease features will not be successful. Better characterization of brain aging in the human population is urgently required to select biomarkers and therapeutic targets that are meaningful to human disease. The generation of detailed and reliable evidence must be addressed before progress toward therapeutic interventions can be made.

Basal Forebrain Atrophy Contributes to Allocentric Navigation Impairment in Alzheimer’s Disease Patients

PubMed Central

Kerbler, Georg M.; Nedelska, Zuzana; Fripp, Jurgen; Laczó, Jan; Vyhnalek, Martin; Lisý, Jiří; Hamlin, Adam S.; Rose, Stephen; Hort, Jakub; Coulson, Elizabeth J.

2015-01-01

The basal forebrain degenerates in Alzheimer’s disease (AD) and this process is believed to contribute to the cognitive decline observed in AD patients. Impairment in spatial navigation is an early feature of the disease but whether basal forebrain dysfunction in AD is responsible for the impaired navigation skills of AD patients is not known. Our objective was to investigate the relationship between basal forebrain volume and performance in real space as well as computer-based navigation paradigms in an elderly cohort comprising cognitively normal controls, subjects with amnestic mild cognitive impairment and those with AD. We also tested whether basal forebrain volume could predict the participants’ ability to perform allocentric- vs. egocentric-based navigation tasks. The basal forebrain volume was calculated from 1.5 T magnetic resonance imaging (MRI) scans, and navigation skills were assessed using the human analog of the Morris water maze employing allocentric, egocentric, and mixed allo/egocentric real space as well as computerized tests. When considering the entire sample, we found that basal forebrain volume correlated with spatial accuracy in allocentric (cued) and mixed allo/egocentric navigation tasks but not the egocentric (uncued) task, demonstrating an important role of the basal forebrain in mediating cue-based spatial navigation capacity. Regression analysis revealed that, although hippocampal volume reflected navigation performance across the entire sample, basal forebrain volume contributed to mixed allo/egocentric navigation performance in the AD group, whereas hippocampal volume did not. This suggests that atrophy of the basal forebrain contributes to aspects of navigation impairment in AD that are independent of hippocampal atrophy. PMID:26441643

Seroprevalence of Neutralizing Antibodies against Human Adenovirus Type-5 and Chimpanzee Adenovirus Type-68 in Cancer Patients.

PubMed

Zhao, Hua; Xu, Can; Luo, Xiaoli; Wei, Feng; Wang, Ning; Shi, Huiying; Ren, Xiubao

2018-01-01

Since the preclinical results about chimpanzee adenovirus serotype-68 (AdC68)-based vaccine showed an encouraging results, it reminded us that AdC68 may be a suitable cancer vaccine vector. Previous study indicated that the seroprevalence of neutralizing antibodies (NAbs) against adenovirus was different between cancer patients and healthy volunteers. Knowledge regarding the prevalence rates of AdC68 NAbs for cancer patients is lacking. Therefore, assessing the preexistence of NAbs against AdC68 in cancer patients could provide useful insights for developing future AdC68-based cancer vaccines. In this study, 440 patients with different pathological types of tumors and 204 healthy adult volunteers were enrolled to evaluate the NAbs against AdC68 and human adenovirus serotype-5 (AdHu5). The seroprevalence of NAbs against AdC68 was much lower than that against AdHu5 in cancer subjects (43.64 vs. 67.05%, P  < 0.01). The seroprevalence rates of NAbs to AdC68 in the cancer subjects were statistically higher than those detected in the healthy adult volunteers (43.64 vs. 23.53%, P  = 0.000). The seroprevalence rates of AdC68 NAbs were much lower in lung, laryngeal, esophageal, and cervical cancer patients compared with oropharyngeal, colon, and rectal cancer patients. Furthermore, the seroprevalence rates of AdC68 NAbs were much lower in lung adenocarcinoma patients than in lung squamous cell carcinoma patients (35.00 vs. 70.00%, P  < 0.05). No significant difference in the AdC68 NAbs among patients with different clinical stages of cancer was detected. The percentage of NAbs against AdC68 was significantly lower than that against AdHu5 ( P  < 0.05) in stage-I, -II, and -III cancer patients. No significant difference between the percentage of NAbs against AdC68 and AdHu5 in the subjects with stage-IV cancer was detected. The study also demonstrated the distribution of AdHu5 and AdC68 NAb titers for the positive samples. It showed that very low NAb titers against AdC68 with respect to AdHu5 in both healthy subjects and cancer subjects, especially in lung, laryngeal, esophageal, gastric, and cervical carcinomas. Also, the titer of NAbs against AdC68 was significantly lower than that against AdHu5 in the same clinical stage and age group ( P  < 0.05). Taken together, the present study showed that NAbs against AdC68 is much lower than AdHu5, especially in lung adenocarcinoma, laryngeal cancer, esophageal cancer, and cervical cancer patients. These results provided strong support for candidating AdC68 as a suitable vector of cancer vaccines.

Intelligent Sensing and Classification in DSR-Based Ad Hoc Networks

NASA Astrophysics Data System (ADS)

Dempsey, Tae; Sahin, Gokhan; Morton, Yu T. (Jade

Wireless ad hoc networks have fundamentally altered today's battlefield, with applications ranging from unmanned air vehicles to randomly deployed sensor networks. Security and vulnerabilities in wireless ad hoc networks have been considered at different layers, and many attack strategies have been proposed, including denial of service (DoS) through the intelligent jamming of the most critical packet types of flows in a network. This paper investigates the effectiveness of intelligent jamming in wireless ad hoc networks using the Dynamic Source Routing (DSR) and TCP protocols and introduces an intelligent classifier to facilitate the jamming of such networks. Assuming encrypted packet headers and contents, our classifier is based solely on the observable characteristics of size, inter-arrival timing, and direction and classifies packets with up to 99.4% accuracy in our experiments.

78 FR 12255 - Airworthiness Directives; Rolls-Royce (1971) Limited, Bristol Engine Division Turbojet Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

...: (202) 493-2251. For service information identified in this AD, contact Rolls-Royce plc, Corporate... received by the closing date and may amend this proposed AD based on those comments. We will post all... this AD, contact Rolls-Royce plc, Corporate Communications, P.O. Box 31, Derby, England, DE248BJ; phone...

The Relationship between Attention Deficit/Hyperactivity Disorder and Aggressive Behaviour in Preschool Boys and Girls

ERIC Educational Resources Information Center

Kakouros, Efthymios; Maniadaki, Katerina; Karaba, Rania

2005-01-01

Research regarding attention deficit/hyperactivity disorder (AD/HD) among preschoolers is limited. This study explored prevalence rates of AD/HD on a community-based sample of preschoolers in Athens. Moreover, it examined the relationship between AD/HD and aggressive behaviour and explored sex differences in this relationship. Nursery teachers…

Old Words, New Meanings: A Study of Trends in Science Librarian Job Ads

ERIC Educational Resources Information Center

Bychowski, Brenna K. H.; Caffrey, Carolyn M.; Costa, Mia C.; Moore, Angela D.; Sudhakaran, Jessamyn; Zhang, Yuening

2010-01-01

Job ads are supposed to provide careful descriptions of the positions being advertised. Based on this premise, an analysis of job ads over time should reveal emerging trends and changes in a profession. The existing literature on science librarianship emphasizes that there are fluctuations in the demand for subject expertise and technology skills…

Analysis of Added Value of Subscores with Respect to Classification

ERIC Educational Resources Information Center

Sinharay, Sandip

2014-01-01

Brennan noted that users of test scores often want (indeed, demand) that subscores be reported, along with total test scores, for diagnostic purposes. Haberman suggested a method based on classical test theory (CTT) to determine if subscores have added value over the total score. One way to interpret the method is that a subscore has added value…

Flight-determined aerodynamic derivatives of the AD-1 oblique-wing research airplane

NASA Technical Reports Server (NTRS)

Sim, A. G.; Curry, R. E.

1984-01-01

The AD-1 is a variable-sweep oblique-wing research airplane that exhibits unconventional stability and control characteristics. In this report, flight-determined and predicted stability and control derivatives for the AD-1 airplane are compared. The predictions are based on both wind tunnel and computational results. A final best estimate of derivatives is presented.

Proposals for Standardizing and Improving the Policy of Adding Points on the Entrance Exam

ERIC Educational Resources Information Center

Yuhong, Deng

2013-01-01

This article reviews policies for adding points on the College Entrance Examination. It analyzes the rationales and specific implementation strategies of various policies for adding points on the entrance exam, as well as their advantages and pitfalls. Based on these observations and analysis, the author also offers policy recommendations on the…

Will Courts Shape Value-Added Methods for Teacher Evaluation? ACT Working Paper Series. WP-2014-2

ERIC Educational Resources Information Center

Croft, Michelle; Buddin, Richard

2014-01-01

As more states begin to adopt teacher evaluation systems based on value-added measures, legal challenges have been filed both seeking to limit the use of value-added measures ("Cook v. Stewart") and others seeking to require more robust evaluation systems ("Vergara v. California"). This study reviews existing teacher evaluation…

Targeting adolescents? The content and frequency of alcoholic and nonalcoholic beverage ads in magazine and video formats November 1999-April 2000.

PubMed

Austin, Erica Weintraub; Hust, Stacey J T

2005-12-01

This study compared alcoholic and nonalcoholic beverage advertising to which adolescents are exposed. A census of beverage advertising (N = 757) in popular magazines and television during November 1999-April 2000 was analyzed. Most alcohol ads appeared in Sports Illustrated (110), Rolling Stone (98), and Playboy (75) and outnumbered nonalcoholic beverage advertising by 3 to 1. Alcohol was almost never associated with dining. Alcohol ads emphasized sexual and social stereotypes and lacked diversity. One of every 6 magazine alcohol ads, and 1 of every 14 video-based ads, appeared to target teenagers. Many similarities existed between alcohol and nonalcohol ads. We conclude that alcohol is advertised heavily to youth through placement and appeals. The fact that themes in alcohol ads frequently parallel those in nonalcoholic beverage ads may further increase youths' receptivity.

Cortical M1 Receptor Concentration Increases Without a Concomitant Change in Function in Alzheimer's Disease

PubMed Central

Overk, Cassia R.; Felder, Christian C.; Tu, Yuan; Schober, Doug A.; Bales, Kelly R.; Wuu, Joanne; Mufson, Elliott J.

2010-01-01

Although the M1 muscarinic receptor is a potential therapeutic target for Alzheimer's disease (AD) based on its wide spread distribution in brain and its association with learning and memory processes, whether its receptor response is altered during the onset of AD remains unclear. A novel [35S]GTPγS binding/immunocapture assay was employed to evaluated changes in M1 receptor function in cortical tissue samples harvested from people who had no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD. M1- function was stable across clinical groups. However, [3H]-oxotremorine-M radioligand binding studies revealed that the concentration of M1 cortical receptors increased significantly between the NCI and AD groups. Although M1 receptor function did not correlate with cognitive function based upon mini-mental status examination (MMSE) or global cognitive score (GCS), functional activity was negatively correlated with the severity of neuropathology determined by Braak staging and NIA-Reagan criteria for AD. Since M1 agonists have the potential to modify the pathologic hallmarks of AD, as well as deficits in cognitive function in animal models of this disease, the present findings provide additional support for targeting the M1 receptor as a potential therapeutic for AD. PMID:20347961

Valence and arousal-based affective evaluations of foods.

PubMed

Woodward, Halley E; Treat, Teresa A; Cameron, C Daryl; Yegorova, Vitaliya

2017-01-01

We investigated the nutrient-specific and individual-specific validity of dual-process models of valenced and arousal-based affective evaluations of foods across the disordered eating spectrum. 283 undergraduate women provided implicit and explicit valence and arousal-based evaluations of 120 food photos with known nutritional information on structurally similar indirect and direct affect misattribution procedures (AMP; Payne et al., 2005, 2008), and completed questionnaires assessing body mass index (BMI), hunger, restriction, and binge eating. Nomothetically, added fat and added sugar enhance evaluations of foods. Idiographically, hunger and binge eating enhance activation, whereas BMI and restriction enhance pleasantness. Added fat is salient for women who are heavier, hungrier, or who restrict; added sugar is influential for less hungry women. Restriction relates only to valence, whereas binge eating relates only to arousal. Findings are similar across implicit and explicit affective evaluations, albeit stronger for explicit, providing modest support for dual-process models of affective evaluation of foods. Copyright © 2016 Elsevier Ltd. All rights reserved.

‘Alzheimer’s Progression Score’: Development of a Biomarker Summary Outcome for AD Prevention Trials

PubMed Central

Leoutsakos, J.-M.; Gross, A.L.; Jones, R.N.; Albert, M.S.; Breitner, J.C.S.

2017-01-01

BACKGROUND Alzheimer’s disease (AD) prevention research requires methods for measurement of disease progression not yet revealed by symptoms. Preferably, such measurement should encompass multiple disease markers. OBJECTIVES Evaluate an item response theory (IRT) model-based latent variable Alzheimer Progression Score (APS) that uses multi-modal disease markers to estimate pre-clinical disease progression. DESIGN Estimate APS scores in the BIOCARD observational study, and in the parallel PREVENT-AD Cohort and its sister INTREPAD placebo-controlled prevention trial. Use BIOCARD data to evaluate whether baseline and early APS trajectory predict later progression to MCI/dementia. Similarly, use longitudinal PREVENT-AD data to assess test measurement invariance over time. Further, assess portability of the PREVENT-AD IRT model to baseline INTREPAD data, and explore model changes when CSF markers are added or withdrawn. SETTING BIOCARD was established in 1995 and participants were followed up to 20 years in Baltimore, USA. The PREVENT-AD and INTREPAD trial cohorts were established between 2011–2015 in Montreal, Canada, using nearly identical entry criteria to enroll high-risk cognitively normal persons aged 60+ then followed for several years. PARTICIPANTS 349 cognitively normal, primarily middle-aged participants in BIOCARD, 125 high-risk participants aged 60+ in PREVENT-AD, and 217 similar subjects in INTREPAD. 106 INTREPAD participants donated up to four serial CSF samples. MEASUREMENTS Global cognitive assessment and multiple structural, functional, and diffusion MRI metrics, sensori-neural tests, and CSF concentrations of tau, Aβ42 and their ratio. RESULTS Both baseline values and early slope of APS scores in BIOCARD predicted later progression to MCI or AD. Presence of CSF variables strongly improved such prediction. A similarly derived APS in PREVENT-AD showed measurement invariance over time and portability to the parallel INTREPAD sample. CONCLUSIONS An IRT-based APS can summarize multimodal information to provide a longitudinal measure of pre-clinical AD progression, and holds promise as an outcome for AD prevention trials. PMID:29034223

'Alzheimer's Progression Score': Development of a Biomarker Summary Outcome for AD Prevention Trials.

PubMed

Leoutsakos, J-M; Gross, A L; Jones, R N; Albert, M S; Breitner, J C S

2016-01-01

Alzheimer's disease (AD) prevention research requires methods for measurement of disease progression not yet revealed by symptoms. Preferably, such measurement should encompass multiple disease markers. Evaluate an item response theory (IRT) model-based latent variable Alzheimer Progression Score (APS) that uses multi-modal disease markers to estimate pre-clinical disease progression. Estimate APS scores in the BIOCARD observational study, and in the parallel PREVENT-AD Cohort and its sister INTREPAD placebo-controlled prevention trial. Use BIOCARD data to evaluate whether baseline and early APS trajectory predict later progression to MCI/dementia. Similarly, use longitudinal PREVENT-AD data to assess test measurement invariance over time. Further, assess portability of the PREVENT-AD IRT model to baseline INTREPAD data, and explore model changes when CSF markers are added or withdrawn. BIOCARD was established in 1995 and participants were followed up to 20 years in Baltimore, USA. The PREVENT-AD and INTREPAD trial cohorts were established between 2011-2015 in Montreal, Canada, using nearly identical entry criteria to enroll high-risk cognitively normal persons aged 60+ then followed for several years. 349 cognitively normal, primarily middle-aged participants in BIOCARD, 125 high-risk participants aged 60+ in PREVENT-AD, and 217 similar subjects in INTREPAD. 106 INTREPAD participants donated up to four serial CSF samples. Global cognitive assessment and multiple structural, functional, and diffusion MRI metrics, sensori-neural tests, and CSF concentrations of tau, Aβ42 and their ratio. Both baseline values and early slope of APS scores in BIOCARD predicted later progression to MCI or AD. Presence of CSF variables strongly improved such prediction. A similarly derived APS in PREVENT-AD showed measurement invariance over time and portability to the parallel INTREPAD sample. An IRT-based APS can summarize multimodal information to provide a longitudinal measure of pre-clinical AD progression, and holds promise as an outcome for AD prevention trials.

The Influence of a Mouthpiece-Based Topography Measurement Device on Electronic Cigarette User's Plasma Nicotine Concentration, Heart Rate, and Subjective Effects Under Directed and Ad Libitum Use Conditions.

PubMed

Spindle, Tory R; Hiler, Marzena M; Breland, Alison B; Karaoghlanian, Nareg V; Shihadeh, Alan L; Eissenberg, Thomas

2017-04-01

Electronic cigarettes e-cigarettes aerosolize a liquid solution often containing nicotine. e-cigarette nicotine delivery may be influenced by user puffing behaviors ("puff topography"). E-cigarette puff topography can be recorded using mouthpiece-based computerized systems. The present study sought to examine the extent to which these systems influence e-cigarette nicotine delivery and other e-cigarette associated acute effects under ad libitum use conditions. Plasma nicotine concentration, heart rate, and subjective effects were assessed in 29 experienced e-cigarette users using their preferred e-cigarette battery and liquid (≥12mg/mL nicotine) in two sessions differing only by the presence of a mouthpiece-based device. In both sessions, participants completed a directed e-cigarette use bout (10 puffs, 30-s interpuff interval) and a 90-min ad libitum bout. Puff topography was recorded in the session with the topography mouthpiece. Plasma nicotine, heart rate, and subjective effects, aside from "Did the e-cigarette Taste Good?" were independent of topography measurement (higher mean taste ratings were observed in the no topography condition). Mean (SEM) plasma nicotine concentration following the ad libitum bout was 34.3ng/mL (4.9) in the no topography condition and 35.7ng/mL (4.3) in the topography condition. Longer puff durations, longer interpuff intervals, and larger puff volumes were observed in the ad libitum relative to the directed bout. E-cigarette use significantly increased plasma nicotine concentration and heart rate while suppressing abstinence symptoms. These effects did not differ when a topography mouthpiece was present. Future studies using ad libitum e-cigarette use bouts would facilitate understanding of e-cigarette toxicant yield. No prior study has examined whether mouthpiece-based topography recording devices influence e-cigarette associated nicotine delivery, heart rate, or subjective effects under ad libitum conditions or assessed ad libitum puff topography in experienced individuals using their preferred e-cigarette battery and liquid with a mouthpiece-based computerized device. E-cigarette use significantly increased plasma nicotine concentration and heart rate while suppressing abstinence symptoms. These effects did not differ when a topography mouthpiece was present. Ad libitum puff topography differed from puff topography recorded during directed puffing. These findings suggest that future studies using ad libitum use bouts would facilitate better understanding of e-cigarette toxicant yield. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Markov Chain-based quantitative study of angular distribution of photons through turbid slabs via isotropic light scattering

NASA Astrophysics Data System (ADS)

Li, Xuesong; Northrop, William F.

2016-04-01

This paper describes a quantitative approach to approximate multiple scattering through an isotropic turbid slab based on Markov Chain theorem. There is an increasing need to utilize multiple scattering for optical diagnostic purposes; however, existing methods are either inaccurate or computationally expensive. Here, we develop a novel Markov Chain approximation approach to solve multiple scattering angular distribution (AD) that can accurately calculate AD while significantly reducing computational cost compared to Monte Carlo simulation. We expect this work to stimulate ongoing multiple scattering research and deterministic reconstruction algorithm development with AD measurements.

Glutamyl-gamma-boronate inhibitors of bacterial Glu-tRNA(Gln) amidotransferase.

PubMed

Decicco, C P; Nelson, D J; Luo, Y; Shen, L; Horiuchi, K Y; Amsler, K M; Foster, L A; Spitz, S M; Merrill, J J; Sizemore, C F; Rogers, K C; Copeland, R A; Harpel, M R

2001-09-17

Analogues of glutamyl-gamma-boronate (1) were synthesized as mechanism-based inhibitors of bacterial Glu-tRNA(Gln) amidotransferase (Glu-AdT) and were designed to engage a putative catalytic serine nucleophile required for the glutaminase activity of the enzyme. Although 1 provides potent enzyme inhibition, structure-activity studies revealed a narrow range of tolerated chemical changes that maintained activity. Nonetheless, growth inhibition of organisms that require Glu-AdT by the most potent enzyme inhibitors appears to validate mechanism-based inhibitor design of Glu-AdT as an approach to antimicrobial development.

Receiver-Based Ad Hoc On Demand Multipath Routing Protocol for Mobile Ad Hoc Networks

PubMed Central

Al-Nahari, Abdulaziz; Mohamad, Mohd Murtadha

2016-01-01

Decreasing the route rediscovery time process in reactive routing protocols is challenging in mobile ad hoc networks. Links between nodes are continuously established and broken because of the characteristics of the network. Finding multiple routes to increase the reliability is also important but requires a fast update, especially in high traffic load and high mobility where paths can be broken as well. The sender node keeps re-establishing path discovery to find new paths, which makes for long time delay. In this paper we propose an improved multipath routing protocol, called Receiver-based ad hoc on demand multipath routing protocol (RB-AOMDV), which takes advantage of the reliability of the state of the art ad hoc on demand multipath distance vector (AOMDV) protocol with less re-established discovery time. The receiver node assumes the role of discovering paths when finding data packets that have not been received after a period of time. Simulation results show the delay and delivery ratio performances are improved compared with AOMDV. PMID:27258013

Performance-based workload assessment: Allocation strategy and added task sensitivity

NASA Technical Reports Server (NTRS)

Vidulich, Michael A.

1990-01-01

The preliminary results of a research program investigating the use of added tasks to evaluate mental workload are reviewed. The focus of the first studies was a reappraisal of the traditional secondary task logic that encouraged the use of low-priority instructions for the added task. It was believed that such low-priority tasks would encourage subjects to split their available resources among the two tasks. The primary task would be assigned all the resources it needed, and any remaining reserve capacity would be assigned to the secondary task. If the model were correct, this approach was expected to combine sensitivity to primary task difficulty with unintrusiveness to primary task performance. The first studies of the current project demonstrated that a high-priority added task, although intrusive, could be more sensitive than the traditional low-priority secondary task. These results suggested that a more appropriate model of the attentional effects associated with added task performance might be based on capacity switching, rather than the traditional optimal allocation model.

Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer's Disease using structural MR and FDG-PET images.

PubMed

Lu, Donghuan; Popuri, Karteek; Ding, Gavin Weiguang; Balachandar, Rakesh; Beg, Mirza Faisal

2018-04-09

Alzheimer's Disease (AD) is a progressive neurodegenerative disease where biomarkers for disease based on pathophysiology may be able to provide objective measures for disease diagnosis and staging. Neuroimaging scans acquired from MRI and metabolism images obtained by FDG-PET provide in-vivo measurements of structure and function (glucose metabolism) in a living brain. It is hypothesized that combining multiple different image modalities providing complementary information could help improve early diagnosis of AD. In this paper, we propose a novel deep-learning-based framework to discriminate individuals with AD utilizing a multimodal and multiscale deep neural network. Our method delivers 82.4% accuracy in identifying the individuals with mild cognitive impairment (MCI) who will convert to AD at 3 years prior to conversion (86.4% combined accuracy for conversion within 1-3 years), a 94.23% sensitivity in classifying individuals with clinical diagnosis of probable AD, and a 86.3% specificity in classifying non-demented controls improving upon results in published literature.

Receiver-Based Ad Hoc On Demand Multipath Routing Protocol for Mobile Ad Hoc Networks.

PubMed

Al-Nahari, Abdulaziz; Mohamad, Mohd Murtadha

2016-01-01

Decreasing the route rediscovery time process in reactive routing protocols is challenging in mobile ad hoc networks. Links between nodes are continuously established and broken because of the characteristics of the network. Finding multiple routes to increase the reliability is also important but requires a fast update, especially in high traffic load and high mobility where paths can be broken as well. The sender node keeps re-establishing path discovery to find new paths, which makes for long time delay. In this paper we propose an improved multipath routing protocol, called Receiver-based ad hoc on demand multipath routing protocol (RB-AOMDV), which takes advantage of the reliability of the state of the art ad hoc on demand multipath distance vector (AOMDV) protocol with less re-established discovery time. The receiver node assumes the role of discovering paths when finding data packets that have not been received after a period of time. Simulation results show the delay and delivery ratio performances are improved compared with AOMDV.

Study of micro piezoelectric vibration generator with added mass and capacitance suitable for broadband vibration

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Qing, E-mail: hqng@163.com; Mao, Xinhua, E-mail: 30400414@qq.com; Chu, Dongliang, E-mail: 569256386@qq.com

This study proposes an optimized frequency adjustment method that uses a micro-cantilever beam-based piezoelectric vibration generator based on a combination of added mass and capacitance. The most important concept of the proposed method is that the frequency adjustment process is divided into two steps: the first is a rough adjustment step that changes the size of the mass added at the end of cantilever to adjust the frequency in a large-scale and discontinuous manner; the second step is a continuous but short-range frequency adjustment via the adjustable added capacitance. Experimental results show that when the initial natural frequency of amore » micro piezoelectric vibration generator is 69.8 Hz, then this natural frequency can be adjusted to any value in the range from 54.2 Hz to 42.1 Hz using the combination of the added mass and the capacitance. This method simply and effectively matches a piezoelectric vibration generator’s natural frequency to the vibration source frequency.« less

Coformer selection based on degradation pathway of drugs: a case study of adefovir dipivoxil-saccharin and adefovir dipivoxil-nicotinamide cocrystals.

PubMed

Gao, Yuan; Gao, Jing; Liu, Ziling; Kan, Hongliang; Zu, Hui; Sun, Wanjin; Zhang, Jianjun; Qian, Shuai

2012-11-15

Adefovir dipivoxil (AD) is a bis(pivaloyloxymethyl) prodrug of adefovir with chemical stability problem. It undergoes two degradation pathways including hydrolysis and dimerization during storage. Pharmaceutical cocrystallization exhibits a promising approach to enhance aqueous solubility as well as physicochemical stability. In this study we attempted to prepare and investigate the physiochemical properties of AD cocrystals, which were formed with two coformers having different acidity and alkalinity (weakly acidic saccharin (SAC) and weakly basic nicotinamide (NCT)). The presence of different coformer molecules along with AD resulted in altered physicochemical properties. AD-SAC cocrystal showed great improvement in solubility and chemical stability, while AD-NCT did not. Several potential factors giving rise to different solid-state properties were summarized. Different coformers resulted in different cocrystal formation, packing style and hydrogen bond formation. This study could provide the coformer selection strategy based on degradation pathways for some unstable drugs in pharmaceutical cocrystal design. Copyright © 2012 Elsevier B.V. All rights reserved.

Analysis of Pervasive Mobile Ad Hoc Routing Protocols

NASA Astrophysics Data System (ADS)

Qadri, Nadia N.; Liotta, Antonio

Mobile ad hoc networks (MANETs) are a fundamental element of pervasive networks and therefore, of pervasive systems that truly support pervasive computing, where user can communicate anywhere, anytime and on-the-fly. In fact, future advances in pervasive computing rely on advancements in mobile communication, which includes both infrastructure-based wireless networks and non-infrastructure-based MANETs. MANETs introduce a new communication paradigm, which does not require a fixed infrastructure - they rely on wireless terminals for routing and transport services. Due to highly dynamic topology, absence of established infrastructure for centralized administration, bandwidth constrained wireless links, and limited resources in MANETs, it is challenging to design an efficient and reliable routing protocol. This chapter reviews the key studies carried out so far on the performance of mobile ad hoc routing protocols. We discuss performance issues and metrics required for the evaluation of ad hoc routing protocols. This leads to a survey of existing work, which captures the performance of ad hoc routing algorithms and their behaviour from different perspectives and highlights avenues for future research.

Specific Features of Executive Dysfunction in Alzheimer-Type Mild Dementia Based on Computerized Cambridge Neuropsychological Test Automated Battery (CANTAB) Test Results.

PubMed

Kuzmickienė, Jurgita; Kaubrys, Gintaras

2016-10-08

BACKGROUND The primary manifestation of Alzheimer's disease (AD) is decline in memory. Dysexecutive symptoms have tremendous impact on functional activities and quality of life. Data regarding frontal-executive dysfunction in mild AD are controversial. The aim of this study was to assess the presence and specific features of executive dysfunction in mild AD based on Cambridge Neuropsychological Test Automated Battery (CANTAB) results. MATERIAL AND METHODS Fifty newly diagnosed, treatment-naïve, mild, late-onset AD patients (MMSE ≥20, AD group) and 25 control subjects (CG group) were recruited in this prospective, cross-sectional study. The CANTAB tests CRT, SOC, PAL, SWM were used for in-depth cognitive assessment. Comparisons were performed using the t test or Mann-Whitney U test, as appropriate. Correlations were evaluated by Pearson r or Spearman R. Statistical significance was set at p<0.05. RESULTS AD and CG groups did not differ according to age, education, gender, or depression. Few differences were found between groups in the SOC test for performance measures: Mean moves (minimum 3 moves): AD (Rank Sum=2227), CG (Rank Sum=623), p<0.001. However, all SOC test time measures differed significantly between groups: SOC Mean subsequent thinking time (4 moves): AD (Rank Sum=2406), CG (Rank Sum=444), p<0.001. Correlations were weak between executive function (SOC) and episodic/working memory (PAL, SWM) (R=0.01-0.38) or attention/psychomotor speed (CRT) (R=0.02-0.37). CONCLUSIONS Frontal-executive functions are impaired in mild AD patients. Executive dysfunction is highly prominent in time measures, but minimal in performance measures. Executive disorders do not correlate with a decline in episodic and working memory or psychomotor speed in mild AD.

The "Power" of Value-Added Thinking: Exploring the Implementation of High-Stakes Teacher Accountability Policies in Rio de Janeiro

ERIC Educational Resources Information Center

Straubhaar, Rolf

2017-01-01

The purpose of this article is to ethnographically document the market-based ideological assumptions of Rio de Janeiro's educational policymakers, and the ways in which those assumptions have informed these policymakers' decision to implement value-added modeling-based teacher evaluation policies. Drawing on the anthropological literature on…

The Value Simulation-Based Learning Added to Machining Technology in Singapore

ERIC Educational Resources Information Center

Fang, Linda; Tan, Hock Soon; Thwin, Mya Mya; Tan, Kim Cheng; Koh, Caroline

2011-01-01

This study seeks to understand the value simulation-based learning (SBL) added to the learning of Machining Technology in a 15-week core subject course offered to university students. The research questions were: (1) How did SBL enhance classroom learning? (2) How did SBL help participants in their test? (3) How did SBL prepare participants for…

What Are Error Rates for Classifying Teacher and School Performance Using Value-Added Models?

ERIC Educational Resources Information Center

Schochet, Peter Z.; Chiang, Hanley S.

2013-01-01

This article addresses likely error rates for measuring teacher and school performance in the upper elementary grades using value-added models applied to student test score gain data. Using a realistic performance measurement system scheme based on hypothesis testing, the authors develop error rate formulas based on ordinary least squares and…

Enhancement of Beaconless Location-Based Routing with Signal Strength Assistance for Ad-Hoc Networks

NASA Astrophysics Data System (ADS)

Chen, Guowei; Itoh, Kenichi; Sato, Takuro

Routing in Ad-hoc networks is unreliable due to the mobility of the nodes. Location-based routing protocols, unlike other protocols which rely on flooding, excel in network scalability. Furthermore, new location-based routing protocols, like, e. g. BLR [1], IGF [2], & CBF [3] have been proposed, with the feature of not requiring beacons in MAC-layer, which improve more in terms of scalability. Such beaconless routing protocols can work efficiently in dense network areas. However, these protocols' algorithms have no ability to avoid from routing into sparse areas. In this article, historical signal strength has been added as a factor into the BLR algorithm, which avoids routing into sparse area, and consequently improves the global routing efficiency.

Automatic Prediction of Conversion from Mild Cognitive Impairment to Probable Alzheimer’s Disease using Structural Magnetic Resonance Imaging

PubMed Central

Nho, Kwangsik; Shen, Li; Kim, Sungeun; Risacher, Shannon L.; West, John D.; Foroud, Tatiana; Jack, Clifford R.; Weiner, Michael W.; Saykin, Andrew J.

2010-01-01

Mild Cognitive Impairment (MCI) is thought to be a precursor to the development of early Alzheimer’s disease (AD). For early diagnosis of AD, the development of a model that is able to predict the conversion of amnestic MCI to AD is challenging. Using automatic whole-brain MRI analysis techniques and pattern classification methods, we developed a model to differentiate AD from healthy controls (HC), and then applied it to the prediction of MCI conversion to AD. Classification was performed using support vector machines (SVMs) together with a SVM-based feature selection method, which selected a set of most discriminating predictors for optimizing prediction accuracy. We obtained 90.5% cross-validation accuracy for classifying AD and HC, and 72.3% accuracy for predicting MCI conversion to AD. These analyses suggest that a classifier trained to separate HC vs. AD has substantial potential for predicting MCI conversion to AD. PMID:21347037

Interactive Vulnerability Analysis Enhancement Results

DTIC Science & Technology

2012-12-01

from JavaEE web based applications to other non-web based Java programs. Technology developed in this effort should be generally applicable to other...Generating a rule is a 2 click process that requires no input from the user. • Task 3: Added support for non- Java EE applications Aspect’s...investigated a variety of Java -based technologies and how IAST can support them. We were successful in adding support for Scala, a popular new language, and

Familiarity-based memory as an early cognitive marker of preclinical and prodromal AD

PubMed Central

Wolk, David A.; Mancuso, Lauren; Kliot, Daria; Arnold, Steven E.; Dickerson, Bradford C.

2013-01-01

There is great interest in the development of cognitive markers that differentiate “normal” age-associated cognitive change from that of Alzheimer's disease (AD) in its prodromal (i.e., mild cognitive impairment; MCI) or even preclinical stages. Dual process models posit that recognition memory is supported by the dissociable processes of recollection and familiarity. Familiarity-based memory has generally been considered to be spared during normal aging, but it remains controversial whether this type of memory is impaired in early AD. Here, we describe findings of estimates of recollection and familiarity in young adults (YA), cognitively normal older adults (CN), and patients with amnestic-MCI (a-MCI). These measures in the CN and a-MCI patients were then related to a structural imaging biomarker of AD that has previously been demonstrated to be sensitive to preclinical and prodromal AD, the Cortical Signature of AD (ADsig). Consistent with much work in the literature, recollection, but not familiarity, was impaired in CN versus YA. Replicating our prior findings, a-MCI patients displayed impairment in both familiarity and recollection. Finally, the familiarity measure was correlated with the ADsig biomarker across the CN and a-MCI group, as well as within the CN adults alone. No other standard psychometric measure was as highly associated with the ADsig, suggesting that familiarity may be a sensitive biomarker of AD-specific brain changes in preclinical and prodromal AD and that it may offer a qualitatively distinct measure of early AD memory impairment relative to normal age-associated change. PMID:23474075

Antibody-based magnetic nanoparticle immunoassay for quantification of Alzheimer's disease pathogenic factor

NASA Astrophysics Data System (ADS)

Kim, Chang-Beom; Choi, Yu Yong; Song, Woo Keun; Song, Ki-Bong

2014-05-01

Alzheimer's disease (AD) is a neurodegenerative disorder that leads to a decline in cognitive and intellectual abilities and an irreversible mental deterioration. Based on multidisciplinary AD research, the most universally accepted hypotheses on AD pathogenesis are the intracerebral aggregate formation of beta-amyloid (Aβ) peptides. According to medical paradigmatic transition from medical treatment to early diagnostic prevention, scientists have considered physiological body fluid as a biomarker medium, in which the promising AD biomarkers could be verified. Recently, use of saliva has been considered as one of the diagnostic fluids over the past decade with meaningful diagnostic potential. We utilized saliva as a biomarker medium to correlate the salivary Aβ levels to AD pathological aspects, especially to the mild cognitive impairment group among AD patients, and to verify our detecting system to be sensitive enough for an early diagnostic tool. The identification of the salivary AD biomarkers using a facile microarraying method would motivate this study with the assistance of magnetically assembled antibody-conjugated nanoparticles and a photomultiplier tube as an optical detector. This simple magnetoimmunoassay system measures the photointensity generated by fluorescence, enables the quantification of the Aβ peptides from AD salivary samples, and consequently classifies the salivary Aβ levels into AD pathological aspects. This method demonstrates a facile approach enabling it to simply detect salivary Aβ peptides at a concentration as low as ˜20 pg/ml. It is expected that our simple magnetoimmunoassay system may have a potential as a detector for low-level Aβ peptides with weak-fluorescence emission.

Lost and forgotten? Orientation versus memory in Alzheimer's disease and frontotemporal dementia.

PubMed

Yew, Belinda; Alladi, Suvarna; Shailaja, Mekala; Hodges, John R; Hornberger, Michael

2013-01-01

Recent studies suggest that significant memory problems are not specific to Alzheimer's disease (AD) but can be also observed in other neurodegenerative conditions, such as behavioral variant frontotemporal dementia (bvFTD). We investigated whether orientation (spatial & temporal) information is a better diagnostic marker for AD compared to memory and whether their atrophy correlates of orientation and memory differ. A large sample (n = 190) of AD patients (n = 73), bvFTD patients (n = 54), and healthy controls (n = 63) underwent testing. A subset of the patients (n = 72) underwent structural imaging using voxel-based morphometry analysis of magnetic resonance brain imaging. Orientation and memory scores from the Addenbrooke's Cognitive Examination showed that AD patients had impaired orientation and memory, while bvFTD patients performing at control level for orientation but had impaired memory. A logistic regression showed that 78% of patients could be classified on the basis of orientation and memory scores alone at clinic presentation. Voxel-based morphometry analysis was conducted using orientation and memory scores as covariates, which showed that the neural correlates for orientation and memory also dissociated with posterior hippocampus cortex being related to orientation in AD, while the anterior hippocampus was associated with memory performance in the AD and bvFTD patients. Orientation and memory measures discriminate AD and bvFTD to a high degree and tap into different hippocampal regions. Disorientation and posterior hippocampus appears therefore specific to AD and will allow clinicians to discriminate AD patients from other neurodegenerative conditions with similar memory deficits at clinic presentation.

Protective Immunity Against a Lethal Respiratory Yersinia pestis Challenge Induced by V Antigen or the F1 Capsular Antigen Incorporated into Adenovirus Capsid

PubMed Central

Boyer, Julie L.; Sofer-Podesta, Carolina; Ang, John; Hackett, Neil R.; Chiuchiolo, Maria J.; Senina, Svetlana; Perlin, David

2010-01-01

Abstract The aerosol form of the bacterium Yersinia pestis causes pneumonic plague, a rapidly fatal disease that is a biothreat if deliberately released. At present, no plague vaccines are available for use in the United States, but subunit vaccines based on the Y. pestis V antigen and F1 capsular protein show promise when administered with adjuvants. In the context that adenovirus (Ad) gene transfer vectors have a strong adjuvant potential related to the ability to directly infect dendritic cells, we hypothesized that modification of the Ad5 capsid to display either the Y. pestis V antigen or the F1 capsular antigen on the virion surface would elicit high V antigen- or F1-specific antibody titers, permit boosting with the same Ad serotype, and provide better protection against a lethal Y. pestis challenge than immunization with equivalent amounts of V or F1 recombinant protein plus conventional adjuvant. We constructed AdYFP-pIX/V and AdLacZ-pIX/F1, E1–, E3– serotype 5 Ad gene transfer vectors containing a fusion of the sequence for either the Y. pestis V antigen or the F1 capsular antigen to the carboxy-terminal sequence of pIX, a capsid protein that can accommodate the entire V antigen (37 kDa) or F1 protein (15 kDa) without disturbing Ad function. Immunization with AdYFP-pIX/V followed by a single repeat administration of the same vector at the same dose resulted in significantly better protection of immunized animals compared with immunization with a molar equivalent amount of purified recombinant V antigen plus Alhydrogel adjuvant. Similarly, immunization with AdLacZ-pIX/F1 in a prime–boost regimen resulted in significantly enhanced protection of immunized animals compared with immunization with a molar-equivalent amount of purified recombinant F1 protein plus adjuvant. These observations demonstrate that Ad vaccine vectors containing pathogen-specific antigens fused to the pIX capsid protein have strong adjuvant properties and stimulate more robust protective immune responses than equivalent recombinant protein-based subunit vaccines administered with conventional adjuvant, suggesting that F1-and/or V-modified capsid Ad-based recombinant vaccines should be considered for development as anti-plague vaccines. PMID:20180652

Mitochondrial base excision repair in mouse synaptosomes during normal aging and in a model of Alzheimer’s disease

PubMed Central

Gredilla, Ricardo; Weissman, Lior; Yang, Jenq-Lin; Bohr, Vilhelm A.; Stevnsner, Tinna

2010-01-01

Brain aging is associated with synaptic decline and cognitive impairment. Increased levels of oxidative DNA base damage and accumulation of mitochondrial DNA (mtDNA) mutations or deletions lead to mitochondrial dysfunction, playing an important role in the aging process and the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). In mitochondria, base excision repair (BER) is the main DNA repair pathway for base modifications such as deamination and oxidation, and constitutes an important mechanism to avoid accumulation of mtDNA mutations. Synaptic function is highly dependent on mitochondria, and in the current study we have investigated BER in synaptosomes of mouse brain during normal aging and in an AD model. Synaptosomes are isolated synapses in membranous structures produced by subcellular fractionation of brain tissue. They include the whole presynaptic terminal as well as portions of the postsynaptic terminal. Synaptosomes contain the molecular machinery necessary for uptake, storage, and release of neurotransmitters, including synaptic vesicles and mitochondria. BER activities were measured in synaptosomal fractions from young and old mice and from pre-symptomatic and symptomatic AD mice harboring mutated APP, Tau and PS1 (3xTgAD). During normal aging, a reduction in the BER capacity was observed in the synaptosomal fraction, which was associated with a decrease in the level of BER proteins. However, we did not observe changes between the synaptosomal BER activities of pre-symptomatic and symptomatic AD mice. Our findings suggest that the age-related reduction in BER capacity in the synaptosomal fraction might contribute to mitochondrial and synaptic dysfunction during aging. The development of AD-like pathology in the 3xTgAD mouse model was, however, not associated with deficiencies of the BER mechanisms in the synaptosomal fraction when the whole brain was analyzed. PMID:20708822

Recruiting Young Gay and Bisexual Men for a Human Papillomavirus Vaccination Intervention Through Social Media: The Effects of Advertisement Content

PubMed Central

Katz, Mira L; Bauermeister, Jose A; Shoben, Abigail B; Paskett, Electra D; McRee, Annie-Laurie

2017-01-01

Background Web-based approaches, specifically social media sites, represent a promising approach for recruiting young gay and bisexual men for research studies. Little is known, however, about how the performance of social media advertisements (ads) used to recruit this population is affected by ad content (ie, image and text). Objective The aim of this study was to evaluate the effects of different images and text included in social media ads used to recruit young gay and bisexual men for the pilot test of a Web-based human papillomavirus (HPV) vaccination intervention. Methods In July and September 2016, we used paid Facebook advertisements to recruit men who were aged 18-25 years, self-identified as gay or bisexual, US resident, and had not received HPV vaccine. A 4x2x2 factorial experiment varied ad image (a single young adult male, a young adult male couple, a group of young adult men, or a young adult male talking to a doctor), content focus (text mentioning HPV or HPV vaccine), and disease framing (text mentioning cancer or a sexually transmitted disease [STD]). Poisson regression determined whether these experimental factors affected ad performance. Results The recruitment campaign reached a total of 35,646 users who viewed ads for 36,395 times. This resulted in an overall unique click-through rate of 2.01% (717/35,646) and an overall conversion rate of 0.66% (241/36,395). Reach was higher for ads that included an image of a couple (incidence rate ratio, IRR=4.91, 95% CI 2.68-8.97, P<.001) or a group (IRR=2.65, 95% CI 1.08-6.50, P=.03) compared with those that included an image of a single person. Ads that included an image of a couple also had a higher conversion rate (IRR=2.56, 95% CI 1.13-5.77, P=.02) than ads that included an image of a single person. Ads with text mentioning an STD had a higher unique click-through rate compared with ads with text mentioning cancer (IRR=1.34, 95% CI 1.06-1.69, P=.01). The campaign cost a total of US $413.72 and resulted in 150 eligible and enrolled individuals (US $2.76 per enrolled participant). Conclusions Facebook ads are a convenient and cost-efficient strategy for reaching and recruiting young gay and bisexual men for a Web-based HPV vaccination intervention. To help optimize ad performance among this population, researchers should consider the importance of the text and image included in the social media recruitment ads. PMID:28576758

The nucleotide sequence and a first generation gene transfer vector of species B human adenovirus serotype 3.

PubMed

Sirena, Dominique; Ruzsics, Zsolt; Schaffner, Walter; Greber, Urs F; Hemmi, Silvio

2005-12-20

Human adenovirus (Ad) serotype 3 causes respiratory infections. It is considered highly virulent, accounting for about 13% of all Ad isolates. We report here the complete Ad3 DNA sequence of 35,343 base pairs (GenBank accession DQ086466). Ad3 shares 96.43% nucleotide identity with Ad7, another virulent subspecies B1 serotype, and 82.56 and 62.75% identity with the less virulent species B2 Ad11 and species C Ad5, respectively. The genomic organization of Ad3 is similar to the other human Ads comprising five early transcription units, E1A, E1B, E2, E3, and E4, two delayed early units IX and IVa2, and the major late unit, in total 39 putative and 7 hypothetical open reading frames. A recombinant E1-deleted Ad3 was generated on a bacterial artificial chromosome. This prototypic virus efficiently transduced CD46-positive rodent and human cells. Our results will help in clarifying the biology and pathology of adenoviruses and enhance therapeutic applications of viral vectors in clinical settings.

String in AdS black hole: A thermo field dynamic approach

NASA Astrophysics Data System (ADS)

Cantcheff, M. Botta; Gadelha, Alexandre L.; Marchioro, Dáfni F. Z.; Nedel, Daniel Luiz

2012-10-01

Based on Maldacena’s description of an eternal anti-de Sitter (AdS) black hole, we reassess the thermo field dynamics (TFD) formalism in the context of the AdS/CFT correspondence. The model studied here involves the maximally extended AdS-Schwarschild solution and two (noninteracting) copies of the conformal field theory (CFT) associated to the global AdS spacetime, along with an extension of the string by imposing natural gluing conditions in the horizon. We show that the gluing conditions in the horizon define a string boundary state which is identified with the TFD thermal vacuum, globally defined in the Kruskal extension of the AdS black hole. We emphasize the connection of this picture with unitary SU(1,1) TFD formulation, and we show that information about the bulk and the conformal boundary is present in the SU(1,1) parameters. Using the unitary SU(1,1) TFD formulation, a canonical prescription for calculating the world sheet real time thermal Green’s function is made, and the entropy associated with the entanglement of the two CFT’s is calculated.

Redirecting adenovirus tropism by genetic, chemical, and mechanical modification of the adenovirus surface for cancer gene therapy.

PubMed

Yoon, A-Rum; Hong, Jinwoo; Kim, Sung Wan; Yun, Chae-Ok

2016-06-01

Despite remarkable advancements, clinical evaluations of adenovirus (Ad)-mediated cancer gene therapies have highlighted the need for improved delivery and targeting. Genetic modification of Ad capsid proteins has been extensively attempted. Although genetic modification enhances the therapeutic potential of Ad, it is difficult to successfully incorporate extraneous moieties into the capsid and the engineering process is laborious. Recently, chemical modification of the Ad surface with nanomaterials and targeting moieties has been found to enhance Ad internalization into the target by both passive and active mechanisms. Alternatively, external stimulus-mediated targeting can result in selective accumulation of Ad in the tumor and prevent dissemination of Ad into surrounding nontarget tissues. In the present review, we discuss various genetic, chemical, and mechanical engineering strategies for overcoming the challenges that hinder the therapeutic efficacy of Ad-based approaches. Surface modification of Ad by genetic, chemical, or mechanical engineering strategies enables Ad to overcome the shortcomings of conventional Ad and enhances delivery efficiency through distinct and unique mechanisms that unmodified Ad cannot mimic. However, although the therapeutic potential of Ad-mediated gene therapy has been enhanced by various surface modification strategies, each strategy still possesses innate limitations that must be addressed, requiring innovative ideas and designs.

Non-invasive screening for Alzheimer's disease by sensing salivary sugar using Drosophila cells expressing gustatory receptor (Gr5a) immobilized on an extended gate ion-sensitive field-effect transistor (EG-ISFET) biosensor.

PubMed

Lau, Hui-Chong; Lee, In-Kyu; Ko, Pan-Woo; Lee, Ho-Won; Huh, Jeung-Soo; Cho, Won-Ju; Lim, Jeong-Ok

2015-01-01

Body fluids are often used as specimens for medical diagnosis. With the advent of advanced analytical techniques in biotechnology, the diagnostic potential of saliva has been the focus of many studies. We recently reported the presence of excess salivary sugars, in patients with Alzheimer's disease (AD). In the present study, we developed a highly sensitive, cell-based biosensor to detect trehalose levels in patient saliva. The developed biosensor relies on the overexpression of sugar sensitive gustatory receptors (Gr5a) in Drosophila cells to detect the salivary trehalose. The cell-based biosensor was built on the foundation of an improved extended gate ion-sensitive field-effect transistor (EG-ISFET). Using an EG-ISFET, instead of a traditional ion-sensitive field-effect transistor (ISFET), resulted in an increase in the sensitivity and reliability of detection. The biosensor was designed with the gate terminals segregated from the conventional ISFET device. This design allows the construction of an independent reference and sensing region for simultaneous and accurate measurements of samples from controls and patients respectively. To investigate the efficacy of the cell-based biosensor for AD screening, we collected 20 saliva samples from each of the following groups: participants diagnosed with AD, participants diagnosed with Parkinson's disease (PD), and a control group composed of healthy individuals. We then studied the response generated from the interaction of the salivary trehalose of the saliva samples and the Gr5a in the immobilized cells on an EG-ISFET sensor. The cell-based biosensor significantly distinguished salivary sugar, trehalose of the AD group from the PD and control groups. Based on these findings, we propose that salivary trehalose, might be a potential biomarker for AD and could be detected using our cell-based EG-ISFET biosensor. The cell-based EG-ISFET biosensor provides a sensitive and direct approach for salivary sugar detection and may be used in the future as a screening method for AD.

Towards Shaping the Field: Theorising the Knowledge in a Formal Course for Academic Developers

ERIC Educational Resources Information Center

Vorster, Jo-Anne; Quinn, Lynn

2015-01-01

In recent years there have been calls both for building the knowledge base of academic development (AD) and for systematic induction of newcomers to the field if AD is to advance as a professional and an academic field. Despite the importance and complexity of AD, induction of novice academic developers remains mostly informal and predominantly…

Reconciling Different Estimates of Teacher Quality Gaps Based on Value Added. CEDR Policy Brief. PB #2016-9

ERIC Educational Resources Information Center

Goldhaber, Dan; Quince, Vanessa; Theobald, Roddy

2016-01-01

This policy brief reviews evidence about the extent to which disadvantaged students are taught by teachers with lower value-added estimates of performance, and seeks to reconcile differences in findings from different studies. We demonstrate that much of the inequity in teacher value added in Washington state is due to differences across different…

Ad Hoc Supervision of General Practice Registrars as a "Community of Practice": Analysis, Interpretation and Re-Presentation

ERIC Educational Resources Information Center

Clement, T.; Brown, J.; Morrison, J.; Nestel, D.

2016-01-01

General practice registrars in Australia undertake most of their vocational training in accredited general practices. They typically see patients alone from the start of their community-based training and are expected to seek timely ad hoc support from their supervisor. Such ad hoc encounters are a mechanism for ensuring patient safety, but also…

A Correlated Random Effects Model for Nonignorable Missing Data in Value-Added Assessment of Teacher Effects

ERIC Educational Resources Information Center

Karl, Andrew T.; Yang, Yan; Lohr, Sharon L.

2013-01-01

Value-added models have been widely used to assess the contributions of individual teachers and schools to students' academic growth based on longitudinal student achievement outcomes. There is concern, however, that ignoring the presence of missing values, which are common in longitudinal studies, can bias teachers' value-added scores.…

Exploring the potential uses of value-added metrics in the context of postgraduate medical education.

PubMed

Gregory, Simon; Patterson, Fiona; Baron, Helen; Knight, Alec; Walsh, Kieran; Irish, Bill; Thomas, Sally

2016-10-01

Increasing pressure is being placed on external accountability and cost efficiency in medical education and training internationally. We present an illustrative data analysis of the value-added of postgraduate medical education. We analysed historical selection (entry) and licensure (exit) examination results for trainees sitting the UK Membership of the Royal College of General Practitioners (MRCGP) licensing examination (N = 2291). Selection data comprised: a clinical problem solving test (CPST); a situational judgement test (SJT); and a selection centre (SC). Exit data was an applied knowledge test (AKT) from MRCGP. Ordinary least squares (OLS) regression analyses were used to model differences in attainment in the AKT based on performance at selection (the value-added score). Results were aggregated to the regional level for comparisons. We discovered significant differences in the value-added score between regional training providers. Whilst three training providers confer significant value-added, one training provider was significantly lower than would be predicted based on the attainment of trainees at selection. Value-added analysis in postgraduate medical education potentially offers useful information, although the methodology is complex, controversial, and has significant limitations. Developing models further could offer important insights to support continuous improvement in medical education in future.

Evaluation of recombinant adenovirus vaccines based on glycoprotein D and truncated UL25 against herpes simplex virus type 2 in mice.

PubMed

Liu, Wei; Zhou, Yan; Wang, Ziyan; Zhang, Zeqiang; Wang, Qizhi; Su, Weiheng; Chen, Yan; Zhang, Yan; Gao, Feng; Jiang, Chunlai; Kong, Wei

2017-05-01

The high prevalence of herpes simplex virus 2 (HSV-2) infections in humans necessitates the development of a safe and effective vaccine that will need to induce vigorous T-cell responses to control viral infection and transmission. We designed rAd-gD2, rAd-gD2ΔUL25, and rAd-ΔUL25 to investigate whether recombinant replication-defective adenoviruses vaccine could induce specific T-cell responses and protect mice against intravaginal HSV-2 challenge compared with FI-HSV-2. In the present study, recombinant adenovirus-based HSV-2 showed higher reductions in mortality and stronger antigen-specific T-cell responses compared with FI-HSV-2 and the severity of genital lesions in mice immunized with rAd-gD2ΔUL25 was significantly decreased by eliciting IFN-γ-secreting T-cell responses compared with rAd-gD2 and rAd-ΔUL25 groups. Our results demonstrated the immunogenicity and protective efficacy of recombinant adenovirus vaccines in acute HSV-2 infection following intravaginal challenge in mice. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Towards Lagrangian formulations of mixed-symmetry higher spin fields on AdS-space within BFV-BRST formalism

NASA Astrophysics Data System (ADS)

Reshetnyak, A. A.

2010-11-01

The spectrum of superstring theory on the AdS 5 × S 5 Ramond-Ramond background in tensionless limit contains integer and half-integer higher-spin fields subject at most to two-rows Young tableaux Y( s 1, s 2). We review the details of a gauge-invariant Lagrangian description of such massive and massless higher-spin fields in anti-de-Sitter spaces with arbitrary dimensions. The procedure is based on the construction of Verma modules, its oscillator realizations and of a BFV-BRST operator for non-linear algebras encoding unitary irreducible representations of AdS group.

Music-based memory enhancement in Alzheimer's disease: promise and limitations.

PubMed

Simmons-Stern, Nicholas R; Deason, Rebecca G; Brandler, Brian J; Frustace, Bruno S; O'Connor, Maureen K; Ally, Brandon A; Budson, Andrew E

2012-12-01

In a previous study (Simmons-Stern, Budson & Ally, 2010), we found that patients with Alzheimer's disease (AD) better recognized visually presented lyrics when the lyrics were also sung rather than spoken at encoding. The present study sought to further investigate the effects of music on memory in patients with AD by making the content of the song lyrics relevant for the daily life of an older adult and by examining how musical encoding alters several different aspects of episodic memory. Patients with AD and healthy older adults studied visually presented novel song lyrics related to instrumental activities of daily living (IADL) that were accompanied by either a sung or a spoken recording. Overall, participants performed better on a memory test of general lyric content for lyrics that were studied sung as compared to spoken. However, on a memory test of specific lyric content, participants performed equally well for sung and spoken lyrics. We interpret these results in terms of a dual-process model of recognition memory such that the general content questions represent a familiarity-based representation that is preferentially sensitive to enhancement via music, while the specific content questions represent a recollection-based representation unaided by musical encoding. Additionally, in a test of basic recognition memory for the audio stimuli, patients with AD demonstrated equal discrimination for sung and spoken stimuli. We propose that the perceptual distinctiveness of musical stimuli enhanced metamemorial awareness in AD patients via a non-selective distinctiveness heuristic, thereby reducing false recognition while at the same time reducing true recognition and eliminating the mnemonic benefit of music. These results are discussed in the context of potential music-based memory enhancement interventions for the care of patients with AD. Published by Elsevier Ltd.

Music-Based Memory Enhancement in Alzheimer’s Disease: Promise and Limitations

PubMed Central

Simmons-Stern, Nicholas R.; Deason, Rebecca G.; Brandler, Brian J.; Frustace, Bruno S.; O’Connor, Maureen K.; Ally, Brandon A.; Budson, Andrew E.

2012-01-01

In a previous study (Simmons-Stern, Budson, & Ally 2010), we found that patients with Alzheimer’s disease (AD) better recognized visually presented lyrics when the lyrics were also sung rather than spoken at encoding. The present study sought to further investigate the effects of music on memory in patients with AD by making the content of the song lyrics relevant for the daily life of an older adult and by examining how musical encoding alters several different aspects of episodic memory. Patients with AD and healthy older adults studied visually presented novel song lyrics related to instrumental activities of daily living (IADL) that were accompanied by either a sung or a spoken recording. Overall, participants performed better on a memory test of general lyric content for lyrics that were studied sung as compared to spoken. However, on a memory test of specific lyric content, participants performed equally well for sung and spoken lyrics. We interpret these results in terms of a dual-process model of recognition memory such that the general content questions represent a familiarity-based representation that is preferentially sensitive to enhancement via music, while the specific content questions represent a recollection-based representation unaided by musical encoding. Additionally, in a test of basic recognition memory for the audio stimuli, patients with AD demonstrated equal discrimination for sung and spoken stimuli. We propose that the perceptual distinctiveness of musical stimuli enhanced metamemorial awareness in AD patients via a non-selective distinctiveness heuristic, thereby reducing false recognition while at the same time reducing true recognition and eliminating the mnemonic benefit of music. These results are discussed in the context of potential music-based memory enhancement interventions for the care of patients with AD. PMID:23000133

Mapping the “What” and “Where” Visual Cortices and Their Atrophy in Alzheimer's Disease: Combined Activation Likelihood Estimation with Voxel-Based Morphometry

PubMed Central

Deng, Yanjia; Shi, Lin; Lei, Yi; Liang, Peipeng; Li, Kuncheng; Chu, Winnie C. W.; Wang, Defeng

2016-01-01

The human cortical regions for processing high-level visual (HLV) functions of different categories remain ambiguous, especially in terms of their conjunctions and specifications. Moreover, the neurobiology of declined HLV functions in patients with Alzheimer's disease (AD) has not been fully investigated. This study provides a functionally sorted overview of HLV cortices for processing “what” and “where” visual perceptions and it investigates their atrophy in AD and MCI patients. Based upon activation likelihood estimation (ALE), brain regions responsible for processing five categories of visual perceptions included in “what” and “where” visions (i.e., object, face, word, motion, and spatial visions) were analyzed, and subsequent contrast analyses were performed to show regions with conjunctive and specific activations for processing these visual functions. Next, based on the resulting ALE maps, the atrophy of HLV cortices in AD and MCI patients was evaluated using voxel-based morphometry. Our ALE results showed brain regions for processing visual perception across the five categories, as well as areas of conjunction and specification. Our comparisons of gray matter (GM) volume demonstrated atrophy of three “where” visual cortices in late MCI group and extensive atrophy of HLV cortices (25 regions in both “what” and “where” visual cortices) in AD group. In addition, the GM volume of atrophied visual cortices in AD and MCI subjects was found to be correlated to the deterioration of overall cognitive status and to the cognitive performances related to memory, execution, and object recognition functions. In summary, these findings may add to our understanding of HLV network organization and of the evolution of visual perceptual dysfunction in AD as the disease progresses. PMID:27445770

The effects of automated artifact removal algorithms on electroencephalography-based Alzheimer's disease diagnosis

PubMed Central

Cassani, Raymundo; Falk, Tiago H.; Fraga, Francisco J.; Kanda, Paulo A. M.; Anghinah, Renato

2014-01-01

Over the last decade, electroencephalography (EEG) has emerged as a reliable tool for the diagnosis of cortical disorders such as Alzheimer's disease (AD). EEG signals, however, are susceptible to several artifacts, such as ocular, muscular, movement, and environmental. To overcome this limitation, existing diagnostic systems commonly depend on experienced clinicians to manually select artifact-free epochs from the collected multi-channel EEG data. Manual selection, however, is a tedious and time-consuming process, rendering the diagnostic system “semi-automated.” Notwithstanding, a number of EEG artifact removal algorithms have been proposed in the literature. The (dis)advantages of using such algorithms in automated AD diagnostic systems, however, have not been documented; this paper aims to fill this gap. Here, we investigate the effects of three state-of-the-art automated artifact removal (AAR) algorithms (both alone and in combination with each other) on AD diagnostic systems based on four different classes of EEG features, namely, spectral, amplitude modulation rate of change, coherence, and phase. The three AAR algorithms tested are statistical artifact rejection (SAR), blind source separation based on second order blind identification and canonical correlation analysis (BSS-SOBI-CCA), and wavelet enhanced independent component analysis (wICA). Experimental results based on 20-channel resting-awake EEG data collected from 59 participants (20 patients with mild AD, 15 with moderate-to-severe AD, and 24 age-matched healthy controls) showed the wICA algorithm alone outperforming other enhancement algorithm combinations across three tasks: diagnosis (control vs. mild vs. moderate), early detection (control vs. mild), and disease progression (mild vs. moderate), thus opening the doors for fully-automated systems that can assist clinicians with early detection of AD, as well as disease severity progression assessment. PMID:24723886

A stable partitioned FSI algorithm for rigid bodies and incompressible flow. Part II: General formulation

NASA Astrophysics Data System (ADS)

Banks, J. W.; Henshaw, W. D.; Schwendeman, D. W.; Tang, Qi

2017-08-01

A stable partitioned algorithm is developed for fluid-structure interaction (FSI) problems involving viscous incompressible flow and rigid bodies. This added-mass partitioned (AMP) algorithm remains stable, without sub-iterations, for light and even zero mass rigid bodies when added-mass and viscous added-damping effects are large. The scheme is based on a generalized Robin interface condition for the fluid pressure that includes terms involving the linear acceleration and angular acceleration of the rigid body. Added mass effects are handled in the Robin condition by inclusion of a boundary integral term that depends on the pressure. Added-damping effects due to the viscous shear forces on the body are treated by inclusion of added-damping tensors that are derived through a linearization of the integrals defining the force and torque. Added-damping effects may be important at low Reynolds number, or, for example, in the case of a rotating cylinder or rotating sphere when the rotational moments of inertia are small. In this second part of a two-part series, the general formulation of the AMP scheme is presented including the form of the AMP interface conditions and added-damping tensors for general geometries. A fully second-order accurate implementation of the AMP scheme is developed in two dimensions based on a fractional-step method for the incompressible Navier-Stokes equations using finite difference methods and overlapping grids to handle the moving geometry. The numerical scheme is verified on a number of difficult benchmark problems.

Automated volumetry of temporal horn of lateral ventricle for detection of Alzheimer's disease in CT scan

NASA Astrophysics Data System (ADS)

Takahashi, Noriyuki; Kinoshita, Toshibumi; Ohmura, Tomomi; Matsuyama, Eri; Toyoshima, Hideto

2018-02-01

The rapid increase in the incidence of Alzheimer's disease (AD) has become a critical issue in low and middle income countries. In general, MR imaging has become sufficiently suitable in clinical situations, while CT scan might be uncommonly used in the diagnosis of AD due to its low contrast between brain tissues. However, in those countries, CT scan, which is less costly and readily available, will be desired to become useful for the diagnosis of AD. For CT scan, the enlargement of the temporal horn of the lateral ventricle (THLV) is one of few findings for the diagnosis of AD. In this paper, we present an automated volumetry of THLV with segmentation based on Bayes' rule on CT images. In our method, first, all CT data sets are normalized into an atlas by using linear affine transformation and non-linear wrapping techniques. Next, a probability map of THLV is constructed in the normalized data. Then, THLV regions are extracted based on Bayes' rule. Finally, the volume of the THLV is evaluated. This scheme was applied to CT scans from 20 AD patients and 20 controls to evaluate the performance of the method for detecting AD. The estimated THLV volume was markedly increased in the AD group compared with the controls (P < .0001), and the area under the receiver operating characteristic curve (AUC) was 0.921. Therefore, this computerized method may have the potential to accurately detect AD on CT images.

Assessing Clinical Microbiology Practice Guidelines: American Society for Microbiology Ad Hoc Committee on Evidence-Based Laboratory Medicine Practice Guidelines Assessment

PubMed Central

Kirn, Thomas J.; Westblade, Lars F.; Humphries, Romney

2017-01-01

ABSTRACT As part of the American Society for Microbiology (ASM) Evidence-Based Laboratory Medicine Practice Guidelines Committee of the Professional Practice Committee, an ad hoc committee was formed in 2014 to assess guidelines published by the committee using an assessment tool, Appraisal of Guidelines for Research Evaluation II (AGREE II). The AGREE II assessment helps reviewers determine whether published guidelines are robust, transparent, and clear in presenting practice recommendations in a standardized manner. Identifying strengths and weaknesses of practice guidelines by ad hoc assessments helps with improving future guidelines through the participation of key stakeholders. This minireview describes the development of the ad hoc committee and results from their review of several ASM best practices guidelines and a non-ASM practice guideline from the Emergency Nurses Association. PMID:28835476

AlzhCPI: A knowledge base for predicting chemical-protein interactions towards Alzheimer's disease.

PubMed

Fang, Jiansong; Wang, Ling; Li, Yecheng; Lian, Wenwen; Pang, Xiaocong; Wang, Hong; Yuan, Dongsheng; Wang, Qi; Liu, Ai-Lin; Du, Guan-Hua

2017-01-01

Alzheimer's disease (AD) is a complicated progressive neurodegeneration disorder. To confront AD, scientists are searching for multi-target-directed ligands (MTDLs) to delay disease progression. The in silico prediction of chemical-protein interactions (CPI) can accelerate target identification and drug discovery. Previously, we developed 100 binary classifiers to predict the CPI for 25 key targets against AD using the multi-target quantitative structure-activity relationship (mt-QSAR) method. In this investigation, we aimed to apply the mt-QSAR method to enlarge the model library to predict CPI towards AD. Another 104 binary classifiers were further constructed to predict the CPI for 26 preclinical AD targets based on the naive Bayesian (NB) and recursive partitioning (RP) algorithms. The internal 5-fold cross-validation and external test set validation were applied to evaluate the performance of the training sets and test set, respectively. The area under the receiver operating characteristic curve (ROC) for the test sets ranged from 0.629 to 1.0, with an average of 0.903. In addition, we developed a web server named AlzhCPI to integrate the comprehensive information of approximately 204 binary classifiers, which has potential applications in network pharmacology and drug repositioning. AlzhCPI is available online at http://rcidm.org/AlzhCPI/index.html. To illustrate the applicability of AlzhCPI, the developed system was employed for the systems pharmacology-based investigation of shichangpu against AD to enhance the understanding of the mechanisms of action of shichangpu from a holistic perspective.

Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer

PubMed Central

Lee, John K.; Bangayan, Nathanael J.; Chai, Timothy; Smith, Bryan A.; Pariva, Tiffany E.; Yun, Sangwon; Vashisht, Ajay; Zhang, Qingfu; Park, Jung Wook; Corey, Eva; Huang, Jiaoti; Wohlschlegel, James; Witte, Owen N.

2018-01-01

Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves a transition from an epithelial to a neurosecretory cancer phenotype. Cell surface markers are often associated with specific cell lineages and differentiation states in normal development and cancer. Here, we show that PrAd and NEPC can be broadly discriminated by cell-surface profiles based on the analysis of prostate cancer gene expression datasets. To overcome a dependence on predictions of human cell-surface genes and an assumed correlation between mRNA levels and protein expression, we integrated transcriptomic and cell-surface proteomic data generated from a panel of prostate cancer cell lines to nominate cell-surface markers associated with these cancer subtypes. FXYD3 and CEACAM5 were validated as cell-surface antigens enriched in PrAd and NEPC, respectively. Given the lack of effective treatments for NEPC, CEACAM5 appeared to be a promising target for cell-based immunotherapy. As a proof of concept, engineered chimeric antigen receptor T cells targeting CEACAM5 induced antigen-specific cytotoxicity in NEPC cell lines. Our findings demonstrate that the surfaceomes of PrAd and NEPC reflect unique cancer differentiation states and broadly represent vulnerabilities amenable to therapeutic targeting. PMID:29686080

Consumer Neuroscience-Based Metrics Predict Recall, Liking and Viewing Rates in Online Advertising.

PubMed

Guixeres, Jaime; Bigné, Enrique; Ausín Azofra, Jose M; Alcañiz Raya, Mariano; Colomer Granero, Adrián; Fuentes Hurtado, Félix; Naranjo Ornedo, Valery

2017-01-01

The purpose of the present study is to investigate whether the effectiveness of a new ad on digital channels (YouTube) can be predicted by using neural networks and neuroscience-based metrics (brain response, heart rate variability and eye tracking). Neurophysiological records from 35 participants were exposed to 8 relevant TV Super Bowl commercials. Correlations between neurophysiological-based metrics, ad recall, ad liking, the ACE metrix score and the number of views on YouTube during a year were investigated. Our findings suggest a significant correlation between neuroscience metrics and self-reported of ad effectiveness and the direct number of views on the YouTube channel. In addition, and using an artificial neural network based on neuroscience metrics, the model classifies (82.9% of average accuracy) and estimate the number of online views (mean error of 0.199). The results highlight the validity of neuromarketing-based techniques for predicting the success of advertising responses. Practitioners can consider the proposed methodology at the design stages of advertising content, thus enhancing advertising effectiveness. The study pioneers the use of neurophysiological methods in predicting advertising success in a digital context. This is the first article that has examined whether these measures could actually be used for predicting views for advertising on YouTube.

Consumer Neuroscience-Based Metrics Predict Recall, Liking and Viewing Rates in Online Advertising

PubMed Central

Guixeres, Jaime; Bigné, Enrique; Ausín Azofra, Jose M.; Alcañiz Raya, Mariano; Colomer Granero, Adrián; Fuentes Hurtado, Félix; Naranjo Ornedo, Valery

2017-01-01

The purpose of the present study is to investigate whether the effectiveness of a new ad on digital channels (YouTube) can be predicted by using neural networks and neuroscience-based metrics (brain response, heart rate variability and eye tracking). Neurophysiological records from 35 participants were exposed to 8 relevant TV Super Bowl commercials. Correlations between neurophysiological-based metrics, ad recall, ad liking, the ACE metrix score and the number of views on YouTube during a year were investigated. Our findings suggest a significant correlation between neuroscience metrics and self-reported of ad effectiveness and the direct number of views on the YouTube channel. In addition, and using an artificial neural network based on neuroscience metrics, the model classifies (82.9% of average accuracy) and estimate the number of online views (mean error of 0.199). The results highlight the validity of neuromarketing-based techniques for predicting the success of advertising responses. Practitioners can consider the proposed methodology at the design stages of advertising content, thus enhancing advertising effectiveness. The study pioneers the use of neurophysiological methods in predicting advertising success in a digital context. This is the first article that has examined whether these measures could actually be used for predicting views for advertising on YouTube. PMID:29163251

Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors

PubMed Central

Chorny, Michael; Fishbein, Ilia; Tengood, Jillian E.; Adamo, Richard F.; Alferiev, Ivan S.; Levy, Robert J.

2013-01-01

Gene therapeutic strategies have shown promise in treating vascular disease. However, their translation into clinical use requires pharmaceutical carriers enabling effective, site-specific delivery as well as providing sustained transgene expression in blood vessels. While replication-deficient adenovirus (Ad) offers several important advantages as a vector for vascular gene therapy, its clinical applicability is limited by rapid inactivation, suboptimal transduction efficiency in vascular cells, and serious systemic adverse effects. We hypothesized that novel zinc oleate-based magnetic nanoparticles (MNPs) loaded with Ad would enable effective arterial cell transduction by shifting vector processing to an alternative pathway, protect Ad from inactivation by neutralizing factors, and allow site-specific gene transfer to arteries treated with stent angioplasty using a 2-source magnetic guidance strategy. Ad-loaded MNPs effectively transduced cultured endothelial and smooth muscle cells under magnetic conditions compared to controls and retained capacity for gene transfer after exposure to neutralizing antibodies and lithium iodide, a lytic agent causing disruption of free Ad. Localized arterial gene expression significantly stronger than in control animal groups was demonstrated after magnetically guided MNP delivery in a rat stenting model 2 and 9 d post-treatment, confirming feasibility of using Ad-loaded MNPs to achieve site-specific transduction in stented blood vessels. In conclusion, Ad-loaded MNPs formed by controlled precipitation of zinc oleate represent a novel delivery system, well-suited for efficient, magnetically targeted vascular gene transfer.—Chorny, M., Fishbein, I., Tengood, J. E., Adamo, R. F., Alferiev, I. S., Levy, R. J. Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors. PMID:23407712

Predicting conversion from MCI to AD using resting-state fMRI, graph theoretical approach and SVM.

PubMed

Hojjati, Seyed Hani; Ebrahimzadeh, Ata; Khazaee, Ali; Babajani-Feremi, Abbas

2017-04-15

We investigated identifying patients with mild cognitive impairment (MCI) who progress to Alzheimer's disease (AD), MCI converter (MCI-C), from those with MCI who do not progress to AD, MCI non-converter (MCI-NC), based on resting-state fMRI (rs-fMRI). Graph theory and machine learning approach were utilized to predict progress of patients with MCI to AD using rs-fMRI. Eighteen MCI converts (average age 73.6 years; 11 male) and 62 age-matched MCI non-converters (average age 73.0 years, 28 male) were included in this study. We trained and tested a support vector machine (SVM) to classify MCI-C from MCI-NC using features constructed based on the local and global graph measures. A novel feature selection algorithm was developed and utilized to select an optimal subset of features. Using subset of optimal features in SVM, we classified MCI-C from MCI-NC with an accuracy, sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve of 91.4%, 83.24%, 90.1%, and 0.95, respectively. Furthermore, results of our statistical analyses were used to identify the affected brain regions in AD. To the best of our knowledge, this is the first study that combines the graph measures (constructed based on rs-fMRI) with machine learning approach and accurately classify MCI-C from MCI-NC. Results of this study demonstrate potential of the proposed approach for early AD diagnosis and demonstrate capability of rs-fMRI to predict conversion from MCI to AD by identifying affected brain regions underlying this conversion. Copyright © 2017 Elsevier B.V. All rights reserved.

Analyzing the genes related to Alzheimer's disease via a network and pathway-based approach.

PubMed

Hu, Yan-Shi; Xin, Juncai; Hu, Ying; Zhang, Lei; Wang, Ju

2017-04-27

Our understanding of the molecular mechanisms underlying Alzheimer's disease (AD) remains incomplete. Previous studies have revealed that genetic factors provide a significant contribution to the pathogenesis and development of AD. In the past years, numerous genes implicated in this disease have been identified via genetic association studies on candidate genes or at the genome-wide level. However, in many cases, the roles of these genes and their interactions in AD are still unclear. A comprehensive and systematic analysis focusing on the biological function and interactions of these genes in the context of AD will therefore provide valuable insights to understand the molecular features of the disease. In this study, we collected genes potentially associated with AD by screening publications on genetic association studies deposited in PubMed. The major biological themes linked with these genes were then revealed by function and biochemical pathway enrichment analysis, and the relation between the pathways was explored by pathway crosstalk analysis. Furthermore, the network features of these AD-related genes were analyzed in the context of human interactome and an AD-specific network was inferred using the Steiner minimal tree algorithm. We compiled 430 human genes reported to be associated with AD from 823 publications. Biological theme analysis indicated that the biological processes and biochemical pathways related to neurodevelopment, metabolism, cell growth and/or survival, and immunology were enriched in these genes. Pathway crosstalk analysis then revealed that the significantly enriched pathways could be grouped into three interlinked modules-neuronal and metabolic module, cell growth/survival and neuroendocrine pathway module, and immune response-related module-indicating an AD-specific immune-endocrine-neuronal regulatory network. Furthermore, an AD-specific protein network was inferred and novel genes potentially associated with AD were identified. By means of network and pathway-based methodology, we explored the pathogenetic mechanism underlying AD at a systems biology level. Results from our work could provide valuable clues for understanding the molecular mechanism underlying AD. In addition, the framework proposed in this study could be used to investigate the pathological molecular network and genes relevant to other complex diseases or phenotypes.

The clinical and economic burden of newly diagnosed Alzheimer's disease in a medicare advantage population.

PubMed

Suehs, Brandon T; Davis, Cralen D; Alvir, Jose; van Amerongen, Derek; Pharmd, Nick C Patel; Joshi, Ashish V; Faison, Warachal E; Shah, Sonali N

2013-06-01

Alzheimer's disease (AD) represents a serious public health issue affecting approximately 5.4 million individuals in the United States and is projected to affect up to 16 million by 2050. This study examined health care resource utilization (HCRU), costs, and comorbidity burden immediately preceding new diagnosis of AD and 2 years after diagnosis. This study utilized a claims-based, retrospective cohort design. Medicare Advantage members newly diagnosed with AD (n = 3374) were compared to matched non-AD controls (n = 6748). All patients with AD were required to have 12 months of continuous enrollment prior to AD diagnosis (International Classification of Diseases, Clinical Modification [ICD-9] 331.0), during which time no diagnosis of AD, a related dementia, or an AD medication was observed. Non-AD controls demonstrated no diagnosis of AD, a related dementia, or a prescription claim for an AD medication treatment during their health plan enrollment. Medical and pharmacy claims data were used to measure HCRU, costs, and comorbidity burden over a period of 36 months (12 months pre-diagnosis and 24 months post-diagnosis). The HCRU and costs were greater for AD members during the year prior to diagnosis and during postdiagnosis years 1 and 2 compared to controls. The AD members also displayed greater comorbidity than their non-AD counterparts during postdiagnosis years 1 and 2, as measured by 2 different comorbidity indices. Members newly diagnosed with AD demonstrated greater HCRU, health care costs, and comorbidity burden compared to matched non-AD controls.

Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization

PubMed Central

Maxfield, Lori F.; Abbink, Peter; Stephenson, Kathryn E.; Borducchi, Erica N.; Ng'ang'a, David; Kirilova, Marinela M.; Paulino, Noelix; Boyd, Michael; Shabram, Paul; Ruan, Qian; Patel, Mayank

2015-01-01

Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors. PMID:26376928

Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization.

PubMed

Maxfield, Lori F; Abbink, Peter; Stephenson, Kathryn E; Borducchi, Erica N; Ng'ang'a, David; Kirilova, Marinela M; Paulino, Noelix; Boyd, Michael; Shabram, Paul; Ruan, Qian; Patel, Mayank; Barouch, Dan H

2015-11-01

Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors. Copyright © 2015, Maxfield et al.

Use of Added Sugars Instead of Total Sugars May Improve the Capacity of the Health Star Rating System to Discriminate between Core and Discretionary Foods.

PubMed

Menday, Hannah; Neal, Bruce; Wu, Jason H Y; Crino, Michelle; Baines, Surinder; Petersen, Kristina S

2017-12-01

The Australian Government has introduced a voluntary front-of-package labeling system that includes total sugar in the calculation. Our aim was to determine the effect of substituting added sugars for total sugars when calculating Health Star Ratings (HSR) and identify whether use of added sugars improves the capacity to distinguish between core and discretionary food products. This study included packaged food and beverage products available in Australian supermarkets (n=3,610). The product categories included in the analyses were breakfast cereals (n=513), fruit (n=571), milk (n=309), non-alcoholic beverages (n=1,040), vegetables (n=787), and yogurt (n=390). Added sugar values were estimated for each product using a validated method. HSRs were then estimated for every product according to the established method using total sugar, and then by substituting added sugar for total sugar. The scoring system was not modified when added sugar was used in place of total sugar in the HSR calculation. Products were classified as core or discretionary based on the Australian Dietary Guidelines. To investigate whether use of added sugar in the HSR algorithm improved the distinction between core and discretionary products as defined by the Australian Dietary Guidelines, the proportion of core products that received an HSR of ≥3.5 stars and the proportion of discretionary products that received an HSR of <3.5 stars, for algorithms based upon total vs added sugars were determined. There were 2,263 core and 1,347 discretionary foods; 1,684 of 3,610 (47%) products contained added sugar (median 8.4 g/100 g, interquartile range=5.0 to 12.2 g). When the HSR was calculated with added sugar instead of total sugar, an additional 166 (7.3%) core products received an HSR of ≥3.5 stars and 103 (7.6%) discretionary products received a rating of ≥3.5 stars. The odds of correctly identifying a product as core vs discretionary were increased by 61% (odds ratio 1.61, 95% CI 1.26 to 2.06; P<0.001) when the algorithm was based on added compared to total sugars. In the six product categories examined, substitution of added sugars for total sugars better aligned the HSR with the Australian Dietary Guidelines. Future work is required to investigate the impact in other product categories. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Is Making a Risky Choice Based on a Weighting and Adding Process? An Eye-Tracking Investigation

ERIC Educational Resources Information Center

Su, Yin; Rao, Li-Lin; Sun, Hong-Yue; Du, Xue-Lei; Li, Xingshan; Li, Shu

2013-01-01

The debate about whether making a risky choice is based on a weighting and adding process has a long history and is still unresolved. To address this long-standing controversy, we developed a comparative paradigm. Participants' eye movements in 2 risky choice tasks that required participants to choose between risky options in single-play and…

Integrated Systems Health Management as an Enabler for Condition Based Maintenance and Autonomic Logistics

DTIC Science & Technology

2015-09-17

turbines , SHM tools, maintenance scheduling, and performance of the SHM system determine the added value of the system of systems (A. Van Horenbeek...J. R., & Pintelon, L. (2013). Quantifying the added value of an imperfectly performing condition monitoring system— Application to a wind turbine ...INTEGRATED SYSTEMS HEALTH MANAGEMENT AS AN ENABLER FOR CONDITION BASED MAINTENANCE AND AUTONOMIC

Hierarchical Interactions Model for Predicting Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD) Conversion

PubMed Central

Li, Han; Liu, Yashu; Gong, Pinghua; Zhang, Changshui; Ye, Jieping

2014-01-01

Identifying patients with Mild Cognitive Impairment (MCI) who are likely to convert to dementia has recently attracted increasing attention in Alzheimer's disease (AD) research. An accurate prediction of conversion from MCI to AD can aid clinicians to initiate treatments at early stage and monitor their effectiveness. However, existing prediction systems based on the original biosignatures are not satisfactory. In this paper, we propose to fit the prediction models using pairwise biosignature interactions, thus capturing higher-order relationship among biosignatures. Specifically, we employ hierarchical constraints and sparsity regularization to prune the high-dimensional input features. Based on the significant biosignatures and underlying interactions identified, we build classifiers to predict the conversion probability based on the selected features. We further analyze the underlying interaction effects of different biosignatures based on the so-called stable expectation scores. We have used 293 MCI subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI) database that have MRI measurements at the baseline to evaluate the effectiveness of the proposed method. Our proposed method achieves better classification performance than state-of-the-art methods. Moreover, we discover several significant interactions predictive of MCI-to-AD conversion. These results shed light on improving the prediction performance using interaction features. PMID:24416143

Altering lipase activity and enantioselectivity in organic media using organo-soluble bases: Implication for rate-limiting proton transfer in acylation step.

PubMed

Chen, Chun-Chi; Chen, Teh-Liang; Tsai, Shau-Wei

2006-06-05

With the hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl esters via a partially purified papaya lipase (PCPL) in water-saturated isooctane as the model system, the enzyme activity, and enantioselectivty is altered by adding a variety of organo-soluble bases that act as either enzyme activators (i.e., TEA, MP, TOA, DPA, PY, and DMA) or enzyme inhibitors (i.e., PDP, DMAP, and PP). Triethylamine (TEA) is selected as the best enzyme activator as 2.24-fold increase of the initial rate for the (S)-ester is obtained when adding 120 mM of the base. By using an expanded Michaelis-Menten mechanism for the acylation step, the kinetic analysis indicates that the proton transfer for the breakdown of tetrahedral intermediates to acyl-enzyme intermediates is the rate-limiting step, or more sensitive than that for the formation of tetrahedral intermediates when the enzyme activators of different pKa are added. However, no correlation for the proton transfers in the acylation step is found when adding the bases acting as enzyme deactivators. Copyright 2006 Wiley Periodicals, Inc.

Functional network connectivity analysis based on partial correlation in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Zhang, Nan; Guan, Xiaoting; Zhang, Yumei; Li, Jingjing; Chen, Hongyan; Chen, Kewei; Fleisher, Adam; Yao, Li; Wu, Xia

2009-02-01

Functional network connectivity (FNC) measures the temporal dependency among the time courses of functional networks. However, the marginal correlation between two networks used in the classic FNC analysis approach doesn't separate the FNC from the direct/indirect effects of other networks. In this study, we proposed an alternative approach based on partial correlation to evaluate the FNC, since partial correlation based FNC can reveal the direct interaction between a pair of networks, removing dependencies or influences from others. Previous studies have demonstrated less task-specific activation and less rest-state activity in Alzheimer's disease (AD). We applied present approach to contrast FNC differences of resting state network (RSN) between AD and normal controls (NC). The fMRI data under resting condition were collected from 15 AD and 16 NC. FNC was calculated for each pair of six RSNs identified using Group ICA, thus resulting in 15 (2 out of 6) pairs for each subject. Partial correlation based FNC analysis indicated 6 pairs significant differences between groups, while marginal correlation only revealed 2 pairs (involved in the partial correlation results). Additionally, patients showed lower correlation than controls among most of the FNC differences. Our results provide new evidences for the disconnection hypothesis in AD.

A Claims-Based Examination of Health Care Costs Among Spouses of Patients With Alzheimer's Disease.

PubMed

Gilden, Daniel M; Kubisiak, Joanna M; Kahle-Wrobleski, Kristin; Ball, Daniel E; Bowman, Lee

2017-06-01

Spouses of Alzheimer's disease patients (AD spouses) may experience substantial health effects associated with their partner's chronic cognitive and behavioral dysfunction. Studies examining associations between the medical experiences of AD spouses in the period before and after their partner's AD diagnosis are limited, particularly those which measure health care resource use and cost. AD patients were identified through multiple Medicare claims containing an AD diagnostic code. Their spouses were identified through special coding in the Medicare eligibility records. The AD spouses were matched demographically to the spouses of Medicare beneficiaries without a history of AD. Longitudinal and annual cross-sectional Medicare cost comparisons utilized log-transformed linear regression. The longitudinal period of observation began 12 months before the AD patient's initial claim listing AD and continued for up to 38 months afterwards. The study identified 16,322 AD spouses. Total per person costs were 24% higher in AD spouses than in the controls ($694/month vs $561/month). AD spouses' excess costs began 3 months before their partners' AD diagnoses and continued for ≥30 months. Being an AD spouse predicted 29% higher Medicare costs after adjustment for chronic health status (P < .001). Increasing AD patient care complexity had a substantial impact on AD spouse Medicare costs (P < .001). This study documents a link between the health status of AD spouses and AD patients. Additional research is required to elicit the mechanism behind the association between AD spouse and AD patient diagnosis. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease.

PubMed

Mattsson, Niklas; Andreasson, Ulf; Zetterberg, Henrik; Blennow, Kaj

2017-05-01

Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias. To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration. In this prospective case-control study, an ultrasensitive assay was used to measure plasma NFL concentration in 193 cognitively healthy controls, 197 patients with mild cognitive impairment (MCI), and 180 patients with AD dementia from the Alzheimer's Disease Neuroimaging Initiative. The study dates were September 7, 2005, to February 13, 2012. The plasma NFL analysis was performed in September 2016. Associations were tested between plasma NFL and diagnosis, Aβ pathologic features, CSF biomarkers of neuronal injury, cognition, brain structure, and metabolism. Among 193 cognitively healthy controls, 197 patients with mild cognitive impairment, and 180 patients with AD with dementia, plasma NFL correlated with CSF NFL (Spearman ρ = 0.59, P < .001). Plasma NFL was increased in patients with MCI (mean, 42.8 ng/L) and patients with AD dementia (mean, 51.0 ng/L) compared with controls (mean, 34.7 ng/L) (P < .001) and had high diagnostic accuracy for patients with AD with dementia vs controls (area under the receiver operating characteristic curve, 0.87, which is comparable to established CSF biomarkers). Plasma NFL was particularly high in patients with MCI and patients with AD dementia with Aβ pathologic features. High plasma NFL correlated with poor cognition and AD-related atrophy (at baseline and longitudinally) and with brain hypometabolism (longitudinally). Plasma NFL is associated with AD diagnosis and with cognitive, biochemical, and imaging hallmarks of the disease. This finding implies a potential usefulness for plasma NFL as a noninvasive biomarker in AD.

Multiple reaction monitoring assay based on conventional liquid chromatography and electrospray ionization for simultaneous monitoring of multiple cerebrospinal fluid biomarker candidates for Alzheimer's disease

PubMed Central

Choi1, Yong Seok; Lee, Kelvin H.

2016-01-01

Alzheimer's disease (AD) is the most common type of dementia, but early and accurate diagnosis remains challenging. Previously, a panel of cerebrospinal fluid (CSF) biomarker candidates distinguishing AD and non-AD CSF accurately (> 90%) was reported. Furthermore, a multiple reaction monitoring (MRM) assay based on nano liquid chromatography tandem mass spectrometry (nLC-MS/MS) was developed to help validate putative AD CSF biomarker candidates including proteins from the panel. Despite the good performance of the MRM assay, wide acceptance may be challenging because of limited availability of nLC-MS/MS systems laboratories. Thus, here, a new MRM assay based on conventional LC-MS/MS is presented. This method monitors 16 peptides representing 16 (of 23) biomarker candidates that belonged to the previous AD CSF panel. A 30-times more concentrated sample than the sample used for the previous study was loaded onto a high capacity trap column, and all 16 MRM transitions showed good linearity (average R2 = 0.966), intra-day reproducibility (average coefficient of variance (CV) = 4.78%), and inter-day reproducibility (average CV = 9.85%). The present method has several advantages such as a shorter analysis time, no possibility of target variability, and no need for an internal standard. PMID:26404792

Drug delivery strategies for Alzheimer's disease treatment.

PubMed

Di Stefano, Antonio; Iannitelli, Antonio; Laserra, Sara; Sozio, Piera

2011-05-01

Current Alzheimer's disease (AD) therapy is based on the administration of the drugs donepezil, galantamine, rivastigmine and memantine. Until disease-modifying therapies become available, further research is needed to develop new drug delivery strategies to ensure ease of administration and treatment persistence. In addition to the conventional oral formulations, a variety of drug delivery strategies applied to the treatment of AD are reviewed in this paper, with a focus on strategies leading to simplified dosage regimens and to providing new pharmacological tools. Alternatives include extended release, orally disintegrating or sublingual formulations, intranasal or short- and long-acting intramuscular or transdermal forms, and nanotechnology-based delivery systems. The advent of new research on molecular mechanisms of AD pathogenesis has outlined new strategies for therapeutic intervention; these include the stimulation of α-secretase cleavage, the inhibition of γ-secretase activity, the use of non-steroidal anti-inflammatory drugs, neuroprotection based on antioxidant therapy, the use of estrogens, NO synthetase inhibitors, and natural agents such as polyphenols. Unfortunately, these compounds might not help patients with end stage AD, but might hopefully slow or stop the disease process in its early stage. Nanotechnologies may prove to be a promising contribution in future AD drug delivery strategies, in particular drug carrier nano- or microsystems, which can limit the side effects of anti-Alzheimer drugs.

Multiple reaction monitoring assay based on conventional liquid chromatography and electrospray ionization for simultaneous monitoring of multiple cerebrospinal fluid biomarker candidates for Alzheimer's disease.

PubMed

Choi, Yong Seok; Lee, Kelvin H

2016-03-01

Alzheimer's disease (AD) is the most common type of dementia, but early and accurate diagnosis remains challenging. Previously, a panel of cerebrospinal fluid (CSF) biomarker candidates distinguishing AD and non-AD CSF accurately (>90 %) was reported. Furthermore, a multiple reaction monitoring (MRM) assay based on nano liquid chromatography tandem mass spectrometry (nLC-MS/MS) was developed to help validate putative AD CSF biomarker candidates including proteins from the panel. Despite the good performance of the MRM assay, wide acceptance may be challenging because of limited availability of nLC-MS/MS systems in laboratories. Thus, here, a new MRM assay based on conventional LC-MS/MS is presented. This method monitors 16 peptides representing 16 (of 23) biomarker candidates that belonged to the previous AD CSF panel. A 30-times more concentrated sample than the sample used for the previous study was loaded onto a high capacity trap column, and all 16 MRM transitions showed good linearity (average R(2) = 0.966), intra-day reproducibility (average coefficient of variance (CV) = 4.78 %), and inter-day reproducibility (average CV = 9.85 %). The present method has several advantages such as a shorter analysis time, no possibility of target variability, and no need for an internal standard.

Detection of subjects and brain regions related to Alzheimer's disease using 3D MRI scans based on eigenbrain and machine learning

PubMed Central

Zhang, Yudong; Dong, Zhengchao; Phillips, Preetha; Wang, Shuihua; Ji, Genlin; Yang, Jiquan; Yuan, Ti-Fei

2015-01-01

Purpose: Early diagnosis or detection of Alzheimer's disease (AD) from the normal elder control (NC) is very important. However, the computer-aided diagnosis (CAD) was not widely used, and the classification performance did not reach the standard of practical use. We proposed a novel CAD system for MR brain images based on eigenbrains and machine learning with two goals: accurate detection of both AD subjects and AD-related brain regions. Method: First, we used maximum inter-class variance (ICV) to select key slices from 3D volumetric data. Second, we generated an eigenbrain set for each subject. Third, the most important eigenbrain (MIE) was obtained by Welch's t-test (WTT). Finally, kernel support-vector-machines with different kernels that were trained by particle swarm optimization, were used to make an accurate prediction of AD subjects. Coefficients of MIE with values higher than 0.98 quantile were highlighted to obtain the discriminant regions that distinguish AD from NC. Results: The experiments showed that the proposed method can predict AD subjects with a competitive performance with existing methods, especially the accuracy of the polynomial kernel (92.36 ± 0.94) was better than the linear kernel of 91.47 ± 1.02 and the radial basis function (RBF) kernel of 86.71 ± 1.93. The proposed eigenbrain-based CAD system detected 30 AD-related brain regions (Anterior Cingulate, Caudate Nucleus, Cerebellum, Cingulate Gyrus, Claustrum, Inferior Frontal Gyrus, Inferior Parietal Lobule, Insula, Lateral Ventricle, Lentiform Nucleus, Lingual Gyrus, Medial Frontal Gyrus, Middle Frontal Gyrus, Middle Occipital Gyrus, Middle Temporal Gyrus, Paracentral Lobule, Parahippocampal Gyrus, Postcentral Gyrus, Posterial Cingulate, Precentral Gyrus, Precuneus, Subcallosal Gyrus, Sub-Gyral, Superior Frontal Gyrus, Superior Parietal Lobule, Superior Temporal Gyrus, Supramarginal Gyrus, Thalamus, Transverse Temporal Gyrus, and Uncus). The results were coherent with existing literatures. Conclusion: The eigenbrain method was effective in AD subject prediction and discriminant brain-region detection in MRI scanning. PMID:26082713

Contributions of Rare Earth Element (La,Ce) Addition to the Impact Toughness of Low Carbon Cast Niobium Microalloyed Steels

NASA Astrophysics Data System (ADS)

Torkamani, Hadi; Raygan, Shahram; Garcia Mateo, Carlos; Rassizadehghani, Jafar; Palizdar, Yahya; San-Martin, David

2018-07-01

In this research Rare Earth elements (RE), La and Ce (200 ppm), were added to a low carbon cast microalloyed steel to disclose their influence on the microstructure and impact toughness. It is suggested that RE are able to change the interaction between the inclusions and matrix during the solidification process (comprising peritectic transformation), which could affect the microstructural features and consequently the impact property; compared to the base steel a clear evolution was observed in nature and morphology of the inclusions present in the RE-added steel i.e. (1) they changed from MnS-based to (RE,Al)(S,O) and RE(S)-based; (2) they obtained an aspect ratio closer to 1 with a lower area fraction as well as a smaller average size. Besides, the microstructural examination of the matrix phases showed that a bimodal type of ferrite grain size distribution exists in both base and RE-added steels, while the mean ferrite grain size was reduced from 12 to 7 μm and the bimodality was redressed in the RE-added steel. It was found that pearlite nodule size decreases from 9 to 6 μm in the RE-added steel; however, microalloying with RE caused only a slight decrease in pearlite volume fraction. After detailed fractography analyses, it was found that, compared to the based steel, the significant enhancement of the impact toughness in RE-added steel (from 63 to 100 J) can be mainly attributed to the differences observed in the nature of the inclusions, the ferrite grain size distribution, and the pearlite nodule size. The presence of carbides (cementite) at ferrite grain boundaries and probable change in distribution of Nb-nanoprecipitation (promoted by RE addition) can be considered as other reasons affecting the impact toughness of steels under investigation.

Contributions of Rare Earth Element (La,Ce) Addition to the Impact Toughness of Low Carbon Cast Niobium Microalloyed Steels

NASA Astrophysics Data System (ADS)

Torkamani, Hadi; Raygan, Shahram; Garcia Mateo, Carlos; Rassizadehghani, Jafar; Palizdar, Yahya; San-Martin, David

2018-03-01

In this research Rare Earth elements (RE), La and Ce (200 ppm), were added to a low carbon cast microalloyed steel to disclose their influence on the microstructure and impact toughness. It is suggested that RE are able to change the interaction between the inclusions and matrix during the solidification process (comprising peritectic transformation), which could affect the microstructural features and consequently the impact property; compared to the base steel a clear evolution was observed in nature and morphology of the inclusions present in the RE-added steel i.e. (1) they changed from MnS-based to (RE,Al)(S,O) and RE(S)-based; (2) they obtained an aspect ratio closer to 1 with a lower area fraction as well as a smaller average size. Besides, the microstructural examination of the matrix phases showed that a bimodal type of ferrite grain size distribution exists in both base and RE-added steels, while the mean ferrite grain size was reduced from 12 to 7 μm and the bimodality was redressed in the RE-added steel. It was found that pearlite nodule size decreases from 9 to 6 μm in the RE-added steel; however, microalloying with RE caused only a slight decrease in pearlite volume fraction. After detailed fractography analyses, it was found that, compared to the based steel, the significant enhancement of the impact toughness in RE-added steel (from 63 to 100 J) can be mainly attributed to the differences observed in the nature of the inclusions, the ferrite grain size distribution, and the pearlite nodule size. The presence of carbides (cementite) at ferrite grain boundaries and probable change in distribution of Nb-nanoprecipitation (promoted by RE addition) can be considered as other reasons affecting the impact toughness of steels under investigation.

Current opinion in Alzheimer's disease therapy by nanotechnology-based approaches.

PubMed

Ansari, Shakeel Ahmed; Satar, Rukhsana; Perveen, Asma; Ashraf, Ghulam Md

2017-03-01

Nanotechnology typically deals with the measuring and modeling of matter at nanometer scale by incorporating the fields of engineering and technology. The most prominent feature of these engineered materials involves their manipulation/modification for imparting new functional properties. The current review covers the most recent findings of Alzheimer's disease (AD) therapeutics based on nanoscience and technology. Current studies involve the application of nanotechnology in developing novel diagnostic and therapeutic tools for neurological disorders. Nanotechnology-based approaches can be exploited for limiting/reversing these diseases for promoting functional regeneration of damaged neurons. These strategies offer neuroprotection by facilitating the delivery of drugs and small molecules more effectively across the blood-brain barrier. Nanotechnology based approaches show promise in improving AD therapeutics. Further replication work on synthesis and surface modification of nanoparticles, longer-term clinical trials, and attempts to increase their impact in treating AD are required.

Information Sharing Modalities for Mobile Ad-Hoc Networks

NASA Astrophysics Data System (ADS)

de Spindler, Alexandre; Grossniklaus, Michael; Lins, Christoph; Norrie, Moira C.

Current mobile phone technologies have fostered the emergence of a new generation of mobile applications. Such applications allow users to interact and share information opportunistically when their mobile devices are in physical proximity or close to fixed installations. It has been shown how mobile applications such as collaborative filtering and location-based services can take advantage of ad-hoc connectivity to use physical proximity as a filter mechanism inherent to the application logic. We discuss the different modes of information sharing that arise in such settings based on the models of persistence and synchronisation. We present a platform that supports the development of applications that can exploit these modes of ad-hoc information sharing and, by means of an example, show how such an application can be realised based on the supported event model.

Voxel-based morphometry in Alzheimers disease and mild cognitive impairment: Systematic review of studies addressing the frontal lobe.

PubMed

Ribeiro, Luís Gustavo; Busatto, Geraldo

2016-01-01

Voxel-based morphometry (VBM) is a useful approach for investigating neurostructural brain changes in dementia. We systematically reviewed VBM studies of Alzheimer's disease (AD) and mild cognitive impairment (MCI), specifically focusing on grey matter (GM) atrophy in the frontal lobe. Two searches were performed on the Pubmed database. A set of exclusion criteria was applied to ensure the selection of only VBM studies that directly investigated GM volume abnormalities in AD and/or MCI patients compared to cognitively normal controls. From a total of 46 selected articles, 35 VBM studies reported GM volume reductions in the frontal lobe. The frontal subregions, where most of the volume reductions were reported, included the inferior, superior and middle frontal gyri, as well as the anterior cingulate gyrus. We also found studies in which reduced frontal GM was detected in MCI patients who converted to AD. In a minority of studies, correlations between frontal GM volumes and behavioural changes or cognitive deficits in AD patients were investigated, with variable findings. Results of VBM studies indicate that the frontal lobe should be regarded as an important brain area when investigating GM volume deficits in association with AD. Frontal GM loss might not be a feature specific to late AD only. Future VBM studies involving large AD samples are warranted to further investigate correlations between frontal volume deficits and both cognitive impairment and neuropsychiatric symptoms.

The contribution of small vessel disease to subtypes of Alzheimer's disease: a study on cerebrospinal fluid and imaging biomarkers.

PubMed

Ferreira, Daniel; Shams, Sara; Cavallin, Lena; Viitanen, Matti; Martola, Juha; Granberg, Tobias; Shams, Mana; Aspelin, Peter; Kristoffersen-Wiberg, Maria; Nordberg, Agneta; Wahlund, Lars-Olof; Westman, Eric

2018-05-30

We investigated whether subtypes of Alzheimer's disease (AD), that is, typical, limbic-predominant, hippocampal-sparing, and minimal atrophy AD, had a specific signature of small vessel disease and neurodegeneration. Four hundred twenty-three clinically diagnosed AD patients were included (161 typical, 121 limbic-predominant, 70 hippocampal-sparing, 71 minimal atrophy). One hundred fifty-six fulfilled a biomarkers-based AD diagnosis. White matter hyperintensities and cerebral microbleeds (CMB) had the highest prevalence in limbic-predominant AD, and the lowest prevalence in minimal atrophy AD. CMB existed evenly in lobar and deep brain areas in limbic-predominant, typical, and hippocampal-sparing AD. In minimal atrophy AD, CMB were mainly located in brain lobar areas. Perivascular spaces in the centrum semiovale were more prevalent in typical AD. Small vessel disease contributed to the prediction of Mini-Mental State Examination. Minimal atrophy AD showed highly pathological levels of cerebrospinal fluid Aß 1-42 , total tau, and phosphorylated tau, in the absence of overt brain atrophy. Cerebral amyloid angiopathy seems to have a stronger contribution to hippocampal-sparing and minimal atrophy AD, whereas hypertensive arteriopathy may have a stronger contribution to typical and limbic-predominant AD. Copyright © 2018 Elsevier Inc. All rights reserved.

Cocaine Analog Coupled to Disrupted Adenovirus: A Vaccine Strategy to Evoke High-titer Immunity Against Addictive Drugs

PubMed Central

Hicks, Martin J; De, Bishnu P; Rosenberg, Jonathan B; Davidson, Jesse T; Moreno, Amira Y; Janda, Kim D; Wee, Sunmee; Koob, George F; Hackett, Neil R; Kaminsky, Stephen M; Worgall, Stefan; Toth, Miklos; Mezey, Jason G; Crystal, Ronald G

2011-01-01

Based on the concept that anticocaine antibodies could prevent inhaled cocaine from reaching its target receptors in the brain, an effective anticocaine vaccine could help reverse cocaine addiction. Leveraging the knowledge that E1−E3− adenovirus (Ad) gene transfer vectors are potent immunogens, we have developed a novel vaccine platform for addictive drugs by covalently linking a cocaine analog to the capsid proteins of noninfectious, disrupted Ad vector. The Ad-based anticocaine vaccine evokes high-titer anticocaine antibodies in mice sufficient to completely reverse, on a persistent basis, the hyperlocomotor activity induced by intravenous administration of cocaine. PMID:21206484

Research on BIM-based building information value chain reengineering

NASA Astrophysics Data System (ADS)

Hui, Zhao; Weishuang, Xie

2017-04-01

The achievement of value and value-added factor to the building engineering information is accomplished through a chain-flow, that is, building the information value chain. Based on the deconstruction of the information chain on the construction information in the traditional information mode, this paper clarifies the value characteristics and requirements of each stage of the construction project. In order to achieve building information value-added, the paper deconstructs the traditional building information value chain, reengineer the information value chain model on the basis of the theory and techniques of BIM, to build value-added management model and analyse the value of the model.

DETAIL OF ORIGINAL DOOR (LOUVERS ADDED LATER) ON THE SOUTH ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

DETAIL OF ORIGINAL DOOR (LOUVERS ADDED LATER) ON THE SOUTH SIDE. VIEW FACING NORTH-NORTHWEST. - U.S. Naval Base, Pearl Harbor, Aviation Storehouse, Vincennes Avenue at Simms Street, Pearl City, Honolulu County, HI

Air Traffic Control Capabilities: Opportunity to Utilize Automated Dependent Surveillance-Broadcast (ADS-B) Equipment on Aircraft for Military Air Traffic Control and Command and Control in Combat and Humanitarian Operations

DTIC Science & Technology

2011-01-21

and as a result reduce aircraft fuel burn and CO2 emissions .”1 EUROCONTROL, representing 32 European nations, is implementing ADS-B under the...ELS) with possible exemptions. By 1 January 2019, they must also be equipped for ADS-B. Canada has also mandated ADS-B4, and nations currently ...based navigational systems 6 like Global Positioning System (GPS). Also, in some domestic overflight or terminal airspaces that currently have 5NM

Mitochondrial DNA sequence analysis of four Alzheimer`s and Parkinson`s disease patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, M.D.; Shoffner, J.M.; Wallace, D.C.

1996-01-22

The mitochondrial DNA (mtDNA) sequence was determined on 3 patients with Alzheimer`s disease (AD) exhibiting AD plus Parkinson`s disease (PD) neuropathologic changes and one patient with PD. Patient mtDNA sequences were compared to the standard Cambridge sequence to identify base changes. In the first AD + PD patient, 2 of the 15 nucleotide substitutions may contribute to the neuropathology, a nucleotide pair (np) 4336 transition in the tRNA{sup Gln} gene found 7.4 times more frequently in patients than in controls, and a unique np 721 transition in the 12S rRNA gene which was not found in 70 other patients ormore » 905 controls. In the second AD + PD patient, 27 nucleotide substitutions were detected, including an np 3397 transition in the ND1 gene which converts a conserved methionine to a valine. In the third AD + PD patient, 2 polymorphic base substitutions frequently found at increased frequency in Leber`s hereditary optic neuropathy patients were observed, an np 4216 transition in ND1 and an np 13708 transition in the ND5 gene. For the PD patient, 2 novel variants were observed among 25 base substitutions, an np 1709 substitution in the 16S rRNA gene and an np 15851 missense mutation in the cytb gene. Further studies will be required to demonstrate a casual role for these base substitutions in neurodegenerative disease. 68 refs., 2 tabs.« less

A novel alphavirus replicon-vectored vaccine delivered by adenovirus induces sterile immunity against classical swine fever.

PubMed

Sun, Yuan; Li, Hong-Yu; Tian, Da-Yong; Han, Qiu-Ying; Zhang, Xin; Li, Na; Qiu, Hua-Ji

2011-10-26

Low efficacy of gene-based vaccines due to inefficient gene delivery and expression has been major bottleneck of their applications. Efforts have been made to improve the efficacy, such as gene gun and electroporation, but the strategies are difficult to put into practical use. In this study, we developed and evaluated an adenovirus-delivered, alphavirus replicon-vectored vaccine (chimeric vector-based vaccine) expressing the E2 gene of classical swine fever virus (CSFV) (rAdV-SFV-E2). Rabbits immunized with rAdV-SFV-E2 developed CSFV-specific antibodies as early as 9 days and as long as 189 days and completely protected from challenge with C-strain. Pigs immunized with rAdV-SFV-E2 (n=5) developed robust humoral and cell-mediated responses to CSFV and were completely protected from subsequent lethal CSFV infection clinically and virologically. The level of immunity and protection induced by rAdV-SFV-E2 was comparable to that provided by the currently used live attenuated vaccine, C-strain. In contrast, both the conventional alphavirus replicon-vectored vaccine pSFV1CS-E2 and conventional adenovirus-vectored vaccine rAdV-E2 provided incomplete protection. The chimeric vector-based vaccine represents the first gene-based vaccine that is able to confer sterile immunity and complete protection against CSFV. The new-concept vaccination strategy may also be valuable in vaccine development against other pathogens. Copyright © 2011 Elsevier Ltd. All rights reserved.

A New Interpretation of Augmented Subscores and Their Added Value in Terms of Parallel Forms

ERIC Educational Resources Information Center

Sinharay, Sandip

2018-01-01

The value-added method of Haberman is arguably one of the most popular methods to evaluate the quality of subscores. The method is based on the classical test theory and deems a subscore to be of added value if the subscore predicts the corresponding true subscore better than does the total score. Sinharay provided an interpretation of the added…

Mobile Security Enclaves

DTIC Science & Technology

2011-09-01

LAI Location Area Identity MANET Mobile Ad - hoc Network MCC Mobile Country Code MCD Mobile Communications Device MNC Mobile Network Code ...tower or present within a geographical area. These conditions relate directly to users who often operate with mobile ad - hoc networks. These types of...infrastructures. First responders can use these mobile base stations to set up their own networks on the fly, similar to mobile ad - hoc networks

When Can Subscores Be Expected to Have Added Value? Results from Operational and Simulated Data. Research Report. ETS RR-10-16

ERIC Educational Resources Information Center

Sinharay, Sandip

2010-01-01

Recently, there has been an increasing level of interest in subscores for their potential diagnostic value. Haberman (2008) suggested a method based on classical test theory to determine whether subscores have added value over total scores. This paper provides a literature review and reports when subscores were found to have added value for…

Cognitive performance on Piagetian tasks by Alzheimer's disease patients.

PubMed

Thornbury, J M

1992-02-01

The purpose of this study was to examine cognitive abilities in Alzheimer's disease (AD) patients using Piaget's child developmental theory. Thirty elderly AD patients and 30 elderly control subjects were given two traditional Piagetian measures, the Infant Psychological Development Scale and the Concrete Operations Test. Half of the AD subjects (15) were in Piaget's sensorimotor or preoperational stages, while the remaining half of the AD subjects and all elderly control subjects were in Piaget's concrete operational stage, chi 2 [1, N = 60] = 17.42, p less than .001. If subsequent studies confirm that AD patients' cognitive characteristics are similar to Piaget's theoretical model, nursing care might be individualized based on mental competence, thus minimizing the commonly observed caregiver overestimation and underestimation of the AD patient's ability to understand and cooperate.

Verbal repetitions and echolalia in Alzheimer's discourse.

PubMed

Da Cruz, Fernanda Miranda

2010-11-01

This article reports on an investigation of echolalic repetition in Alzheimer's disease (AD). A qualitative analysis of data from spontaneous conversations with MHI, a woman with AD, is presented. The data come from the DALI Corpus, a corpus of spontaneous conversations involving subjects with AD. This study argues that echolalic effects can be explained through an analysis of their formal linguistic aspects, such as intonational-prosodic and enunciative-syntactic features. The analysis shows that the description of echolalic repetitions in these terms can help find parameters for the description of the linguistic and communicative characteristics of AD. This analysis even shows how a previous speech turn serves as a base for the elaboration of the next turn by the participant with AD. It also contributes to the understanding of echolalic productions in AD.

Enhancing the effectiveness of antismoking messages via self-congruent appeals.

PubMed

Chang, Chingching

2009-01-01

A self-congruent effect model was applied to understand adolescents' responses to antismoking advertising that referred to the self or others. Experiment 1 showed that self-referring ads generated more negative smoking attitudes than other-referring ads among adolescents with independent self-construals, whereas other-referring ads generated more negative smoking attitudes than self-referring ads among adolescents with interdependent self-construals. A survey further showed that smokers rated themselves higher on a measure of independent self-construal than nonsmokers. Experiment 2 then found that self-referring ads are more effective than other-referring ads for smokers, who have independent self-construals. Findings supported the idea that health communication campaign designers can maximize message effectiveness by developing different messages for different target segments of the population based on their self-construals.

Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

PubMed

Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

2018-03-15

Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug discovery and play an important role in optimizing multi-target drug discovery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Declining functional connectivity and changing hub locations in Alzheimer's disease: an EEG study.

PubMed

Engels, Marjolein M A; Stam, Cornelis J; van der Flier, Wiesje M; Scheltens, Philip; de Waal, Hanneke; van Straaten, Elisabeth C W

2015-08-20

EEG studies have shown that patients with Alzheimer's disease (AD) have weaker functional connectivity than controls, especially in higher frequency bands. Furthermore, active regions seem more prone to AD pathology. How functional connectivity is affected in AD subgroups of disease severity and how network hubs (highly connected brain areas) change is not known. We compared AD patients with different disease severity and controls in terms of functional connections, hub strength and hub location. We studied routine 21-channel resting-state electroencephalography (EEG) of 318 AD patients (divided into tertiles based on disease severity: mild, moderate and severe AD) and 133 age-matched controls. Functional connectivity between EEG channels was estimated with the Phase Lag Index (PLI). From the PLI-based connectivity matrix, the minimum spanning tree (MST) was derived. For each node (EEG channel) in the MST, the betweenness centrality (BC) was computed, a measure to quantify the relative importance of a node within the network. Then we derived color-coded head plots based on BC values and calculated the center of mass (the exact middle had x and y values of 0). A shifting of the hub locations was defined as a shift of the center of mass on the y-axis across groups. Multivariate general linear models with PLI or BC values as dependent variables and the groups as continuous variables were used in the five conventional frequency bands. We found that functional connectivity decreases with increasing disease severity in the alpha band. All, except for posterior, regions showed increasing BC values with increasing disease severity. The center of mass shifted from posterior to more anterior regions with increasing disease severity in the higher frequency bands, indicating a loss of relative functional importance of the posterior brain regions. In conclusion, we observed decreasing functional connectivity in the posterior regions, together with a shifted hub location from posterior to central regions with increasing AD severity. Relative hub strength decreases in posterior regions while other regions show a relative rise with increasing AD severity, which is in accordance with the activity-dependent degeneration theory. Our results indicate that hubs are disproportionally affected in AD.

[Item function analysis on the Quality of Life-Alzheimer's Disease(QOL-AD)Chinese version, based on the Item Response Theory(IRT)].

PubMed

Wan, Li-ping; He, Run-lian; Ai, Yong-mei; Zhang, Hui-min; Xing, Min; Yang, Lin; Song, Yan-long; Yu, Hong-mei

2013-07-01

To introduce the Item Function Analysis(IFA) of Quality of Life- Alzheimer's disease(QOL-AD)Chinese version and to explore the feasibility of its application on Chinese patients with AD. Two hundred AD patients were interviewed and assessed by QOL-AD, through the stratified cluster sampling method. Multilog 7.03. was used for Item Function Analysis. Difference scale(a), difficulty scale(b)and Item Characteristic Curve(ICC) of each item of QOL-AD were provided. Different scales of the item 1, 7 were below 0.6, while all the others were above 0.6. As for ICC. The first and last lines for the other items were monotonic in which the two in between were in inverted V-shape, with very steep slopes, except for the item 1 and 7. Results form the IFA showed that QOL-AD was applicable to be used in the Chinese patients with AD.

Human adenovirus serotype 12 virion precursors pMu and pVI are cleaved at amino-terminal and carboxy-terminal sites that conform to the adenovirus 2 endoproteinase cleavage consensus sequence.

PubMed

Freimuth, P; Anderson, C W

1993-03-01

The sequence of a 1158-base pair fragment of the human adenovirus serotype 12 (Ad12) genome was determined. This segment encodes the precursors for virion components Mu and VI. Both Ad12 precursors contain two sequences that conform to a consensus sequence motif for cleavage by the endoproteinase of adenovirus 2 (Ad2). Analysis of the amino terminus of VI and of the peptide fragments found in Ad12 virions demonstrated that these sites are cleaved during Ad12 maturation. This observation suggests that the recognition motif for adenovirus endoproteinases is highly conserved among human serotypes. The adenovirus 2 endoproteinase polypeptide requires additional co-factors for activity (C. W. Anderson, Protein Expression Purif., 1993, 4, 8-15). Synthetic Ad12 or Ad2 pVI carboxy-terminal peptides each permitted efficient cleavage of an artificial endoproteinase substrate by recombinant Ad2 endoproteinase polypeptide.

ADMultiImg: a novel missing modality transfer learning based CAD system for diagnosis of MCI due to AD using incomplete multi-modality imaging data

NASA Astrophysics Data System (ADS)

Liu, Xiaonan; Chen, Kewei; Wu, Teresa; Weidman, David; Lure, Fleming; Li, Jing

2018-02-01

Alzheimer's Disease (AD) is the most common cause of dementia and currently has no cure. Treatments targeting early stages of AD such as Mild Cognitive Impairment (MCI) may be most effective to deaccelerate AD, thus attracting increasing attention. However, MCI has substantial heterogeneity in that it can be caused by various underlying conditions, not only AD. To detect MCI due to AD, NIA-AA published updated consensus criteria in 2011, in which the use of multi-modality images was highlighted as one of the most promising methods. It is of great interest to develop a CAD system based on automatic, quantitative analysis of multi-modality images and machine learning algorithms to help physicians more adequately diagnose MCI due to AD. The challenge, however, is that multi-modality images are not universally available for many patients due to cost, access, safety, and lack of consent. We developed a novel Missing Modality Transfer Learning (MMTL) algorithm capable of utilizing whatever imaging modalities are available for an MCI patient to diagnose the patient's likelihood of MCI due to AD. Furthermore, we integrated MMTL with radiomics steps including image processing, feature extraction, and feature screening, and a post-processing for uncertainty quantification (UQ), and developed a CAD system called "ADMultiImg" to assist clinical diagnosis of MCI due to AD using multi-modality images together with patient demographic and genetic information. Tested on ADNI date, our system can generate a diagnosis with high accuracy even for patients with only partially available image modalities (AUC=0.94), and therefore may have broad clinical utility.

Food combination and Alzheimer disease risk: a protective diet.

PubMed

Gu, Yian; Nieves, Jeri W; Stern, Yaakov; Luchsinger, Jose A; Scarmeas, Nikolaos

2010-06-01

To assess the association between food combination and Alzheimer disease (AD) risk. Because foods are not consumed in isolation, dietary pattern (DP) analysis of food combination, taking into account the interactions among food components, may offer methodological advantages. Prospective cohort study. Northern Manhattan, New York, New York. Two thousand one hundred forty-eight community-based elderly subjects (aged > or = 65 years) without dementia in New York provided dietary information and were prospectively evaluated with the same standardized neurological and neuropsychological measures approximately every 1.5 years. Using reduced rank regression, we calculated DPs based on their ability to explain variation in 7 potentially AD-related nutrients: saturated fatty acids, monounsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-6 polyunsaturated fatty acids, vitamin E, vitamin B(12), and folate. The associations of reduced rank regression-derived DPs with AD risk were then examined using a Cox proportional hazards model. Main Outcome Measure Incident AD risk. Two hundred fifty-three subjects developed AD during a follow-up of 3.9 years. We identified a DP strongly associated with lower AD risk: compared with subjects in the lowest tertile of adherence to this pattern, the AD hazard ratio (95% confidence interval) for subjects in the highest DP tertile was 0.62 (0.43-0.89) after multivariable adjustment (P for trend = .01). This DP was characterized by higher intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, and dark and green leafy vegetables and a lower intake of high-fat dairy products, red meat, organ meat, and butter. Simultaneous consideration of previous knowledge regarding potentially AD-related nutrients and multiple food groups can aid in identifying food combinations that are associated with AD risk.

Combining select neuropsychological assessment with blood-based biomarkers to detect mild Alzheimer's disease: a molecular neuropsychology approach.

PubMed

Edwards, Melissa; Balldin, Valerie Hobson; Hall, James; O'Bryant, Sid

2014-01-01

Current work has sought to establish a rapid and cost effective means of screening for Alzheimer's disease (AD) with the most recent findings showing utility of integrating blood-based biomarkers with cognitive measures. The current project sought to create a combined biomarker-cognitive profile to detect mild AD. Data was analyzed from 266 participants (129 AD cases [Early AD n = 93; Very Early AD n = 36]; 137 controls) enrolled in the Texas Alzheimer's Research and Care Consortium (TARCC). Non-fasting serum samples were collected from each participant and assayed via a multi-plex biomarker assay platform using electrochemiluminescence. Logistic Regression was utilized to detect early AD using two serum biomarkers (TNFα and IL7), demographic information (age), and one neuropsychological measure (Clock 4-point) as predictor variable. Disease severity was determined via Clinical Dementia Rating (CDR) scale global scores. In the total sample (all levels of CDR scores), the combination of biomarkers, cognitive test score, and demographics yielded the obtained sensitivity (SN) of 0.94, specificity (SP) of 0.90, and an overall accuracy of 0.92. When examining early AD cases (i.e.m CDR = 0.5-1), the biomarker-cognitive profile yielded SN of 0.94, SP of 0.85, and an overall accuracy of 0.91. When restricted to very early AD cases (i.e., CDR = 0.5), the biomarker-cognitive profile yielded SN of 0.97 and SP of 0.72, with an overall accuracy of 0.91. The combination of demographics, two biomarkers, and one cognitive test created a biomarker-cognitive profile that was highly accurate in detecting the presence of AD, even in the very early stages.

Risk for self-reported anorexia or bulimia nervosa based on drive for thinness and negative affect clusters/dimensions during adolescence: A three-year prospective study of the TChAD cohort.

PubMed

Peñas-Lledó, Eva; Bulik, Cynthia M; Lichtenstein, Paul; Larsson, Henrik; Baker, Jessica H

2015-09-01

This study explored the cross-sectional and predictive effect of drive for thinness and/or negative affect scores on the development of self-reported anorexia nervosa (AN) and bulimia nervosa (BN). K-means were used to cluster the Eating Disorder Inventory-Drive for Thinness (DT) and Child Behavior Checklist Anxious/Depressed (A/D) scores from 615 unrelated female twins at age 16-17. Logistic regressions were used to assess the effect of these clusters on self-reported eating disorder diagnosis at ages 16-17 (n = 565) and 19-20 (n = 451). DT and A/D scores were grouped into four clusters: Mild (scores lower than 90th percentile on both scales), DT (higher scores only on DT), A/D (higher scores only on A/D), and DT-A/D (higher scores on both the DT and A/D scales). DT and DT-A/D clusters at age 16-17 were associated cross-sectionally with AN and both cross-sectionally and longitudinally with BN. The DT-A/D cluster had the highest prevalence of AN at follow-up compared with all other clusters. Similarly, an interaction was observed between DT and A/D that predicted risk for AN. Having elevated DT and A/D scores may increase risk for eating disorder symptomatology above and beyond a high score on either alone. Findings suggest that cluster modeling based on DT and A/D may be useful to inform novel and useful intervention strategies for AN and BN in adolescents. © 2015 Wiley Periodicals, Inc.

Risk for self-reported anorexia or bulimia nervosa based on drive for thinness and negative affect clusters/dimensions during adolescence: A three-year prospective study of the TChAD cohort

PubMed Central

Peñas-Lledó, Eva; Bulik, Cynthia M.; Lichtenstein, Paul; Larsson, Henrik; Baker, Jessica H.

2015-01-01

Objective The present study explored the cross-sectional and predictive effect of drive for thinness and/or negative affect scores on the development of self-reported anorexia nervosa (AN) and bulimia nervosa (BN). Method K-means were used to cluster the Eating Disorder Inventory-Drive for Thinness (DT) and Child Behavior Checklist Anxious/Depressed (A/D) scores from 615 unrelated female twins at age 16–17. Logistic regressions were used to assess the effect of these clusters on self-reported eating disorder diagnosis at ages 16–17 (n=565) and 19–20 (n=451). Results DT and A/D scores were grouped into four clusters: Mild (scores lower than 90th percentile on both scales), DT (higher scores only on DT), A/D (higher scores only on A/D), and DT-A/D (higher scores on both the DT and A/D scales). DT and DT-A/D clusters at age 16–17 were associated cross-sectionally with AN and both cross-sectionally and longitudinally with BN. The DT-A/D cluster had the highest prevalence of AN at follow-up compared with all other clusters. Similarly, an interaction was observed between DT and A/D that predicted risk for AN. Discussion Having elevated DT and A/D scores may increase risk for eating disorder symptomatology above and beyond a high score on either alone. Findings suggest that cluster modeling based on DT and A/D may be useful to inform novel and useful intervention strategies for AN and BN in adolescents. PMID:26013185

Replicating Single-Cycle Adenovirus Vectors Generate Amplified Influenza Vaccine Responses.

PubMed

Crosby, Catherine M; Matchett, William E; Anguiano-Zarate, Stephanie S; Parks, Christopher A; Weaver, Eric A; Pease, Larry R; Webby, Richard J; Barry, Michael A

2017-01-15

Head-to-head comparisons of conventional influenza vaccines with adenovirus (Ad) gene-based vaccines demonstrated that these viral vectors can mediate more potent protection against influenza virus infection in animal models. In most cases, Ad vaccines are engineered to be replication-defective (RD-Ad) vectors. In contrast, replication-competent Ad (RC-Ad) vaccines are markedly more potent but risk causing adenovirus diseases in vaccine recipients and health care workers. To harness antigen gene replication but avoid production of infectious virions, we developed "single-cycle" adenovirus (SC-Ad) vectors. Previous work demonstrated that SC-Ads amplify transgene expression 100-fold and produce markedly stronger and more persistent immune responses than RD-Ad vectors in Syrian hamsters and rhesus macaques. To test them as potential vaccines, we engineered RD and SC versions of adenovirus serotype 6 (Ad6) to express the hemagglutinin (HA) gene from influenza A/PR/8/34 virus. We show here that it takes approximately 33 times less SC-Ad6 than RD-Ad6 to produce equal amounts of HA antigen in vitro SC-Ad produced markedly higher HA binding and hemagglutination inhibition (HAI) titers than RD-Ad in Syrian hamsters. SC-Ad-vaccinated cotton rats had markedly lower influenza titers than RD-Ad-vaccinated animals after challenge with influenza A/PR/8/34 virus. These data suggest that SC-Ads may be more potent vaccine platforms than conventional RD-Ad vectors and may have utility as "needle-free" mucosal vaccines. Most adenovirus vaccines that are being tested are replication-defective adenoviruses (RD-Ads). This work describes testing newer single-cycle adenovirus (SC-Ad) vectors that replicate transgenes to amplify protein production and immune responses. We show that SC-Ads generate markedly more influenza virus hemagglutinin protein and require substantially less vector to generate the same immune responses as RD-Ad vectors. SC-Ads therefore hold promise to be more potent vectors and vaccines than current RD-Ad vectors. Copyright © 2017 Crosby et al.

Blood Ammonia as a Possible Etiological Agent for Alzheimer’s Disease

PubMed Central

Jin, Yan Yan; Singh, Parul; Chung, Hea-Jong; Hong, Seong-Tschool

2018-01-01

Alzheimer’s disease (AD), characterized by cognitive decline and devastating neurodegeneration, is the most common age-related dementia. Since AD is a typical example of a complex disease that is affected by various genetic and environmental factors, various factors could be involved in preventing and/or treating AD. Extracellular accumulation of beta-amyloid peptide (Aβ) and intracellular accumulation of tau undeniably play essential roles in the etiology of AD. However, interestingly enough, medications targeting Aβ or tau all failed and the only clinically efficient medications for AD are drugs targeting the cholinergic pathway. Also, a very intriguing discovery in AD is that the Mediterranean diet (MeDi), containing an unusually large quantity of Lactobacilli, is very effective in preventing AD. Based on recently emerging findings, it is our opinion that the reduction of blood ammonia levels by Lactobacilli in MeDi is the therapeutic agent of MeDi for AD. The recent evidence of Lactobacilli lowering blood ammonia level not only provides a link between AD and MeDi but also provides a foundation of pharmabiotics for hyperammonemia as well as various neurological diseases. PMID:29734664

Blood Ammonia as a Possible Etiological Agent for Alzheimer's Disease.

PubMed

Jin, Yan Yan; Singh, Parul; Chung, Hea-Jong; Hong, Seong-Tschool

2018-05-04

Alzheimer’s disease (AD), characterized by cognitive decline and devastating neurodegeneration, is the most common age-related dementia. Since AD is a typical example of a complex disease that is affected by various genetic and environmental factors, various factors could be involved in preventing and/or treating AD. Extracellular accumulation of beta-amyloid peptide (Aβ) and intracellular accumulation of tau undeniably play essential roles in the etiology of AD. However, interestingly enough, medications targeting Aβ or tau all failed and the only clinically efficient medications for AD are drugs targeting the cholinergic pathway. Also, a very intriguing discovery in AD is that the Mediterranean diet (MeDi), containing an unusually large quantity of Lactobacilli, is very effective in preventing AD. Based on recently emerging findings, it is our opinion that the reduction of blood ammonia levels by Lactobacilli in MeDi is the therapeutic agent of MeDi for AD. The recent evidence of Lactobacilli lowering blood ammonia level not only provides a link between AD and MeDi but also provides a foundation of pharmabiotics for hyperammonemia as well as various neurological diseases.

Patient-centered care as value-added service by compounding pharmacists.

PubMed

McPherson, Timothy B; Fontane, Patrick E; Day, Jonathan R

2013-01-01

The term "value-added" is widely used to describe business and professional services that complement a product or service or that differentiate it from competing products and services. The objective of this study was to determine compounding pharmacists' self-perceptions of the value-added services they provide. A web-based survey method was used. Respondents' perceptions of their most important value-added service frequently fell into one of two categories: (1) enhanced pharmacist contribution to developing and implementing patient therapeutic plans and (2) providing customized medications of high pharmaceutical quality. The results were consistent with a hybrid community clinical practice model for compounding pharmacists wherein personalization of the professional relationship is the value-added characteristic.

Media mating I: newspaper "personals" ads of homosexual men.

PubMed

Laner, M R; Kamel, G W

1977-01-01

Based on a design used in previous research with heterosexuals "Personals" advertisements, this study reports a content analysis of 359 ads placed by male homosexuals. Following exchange theory, it was hypothesized that, as with heterosexuals, a favorable presentation of self would characterize the advertisements. Further hypotheses predicted that homosexual ads would be more frank than are heterosexual ads and more specific about goals for desired relationships, and that homosexual ads would reflect the "virilization" of the male homosexual subculture. All predictions were strongly supported. The overtly sexual explicitness of many of the advertisements was explained on the basis of differences between same- and cross-sex relationships, and male/female differences in conceptualizing "love."

The Multi-energy High precision Data Processor Based on AD7606

NASA Astrophysics Data System (ADS)

Zhao, Chen; Zhang, Yanchi; Xie, Da

2017-11-01

This paper designs an information collector based on AD7606 to realize the high-precision simultaneous acquisition of multi-source information of multi-energy systems to form the information platform of the energy Internet at Laogang with electricty as its major energy source. Combined with information fusion technologies, this paper analyzes the data to improve the overall energy system scheduling capability and reliability.

GUIDELINES OF CARE FOR THE MANAGEMENT OF ATOPIC DERMATITIS

PubMed Central

Eichenfield, Lawrence F.; Tom, Wynnis L.; Berger, Timothy G.; Krol, Alfons; Paller, Amy S.; Schwarzenberger, Kathryn; Bergman, James N.; Chamlin, Sarah L.; Cohen, David E.; Cooper, Kevin D.; Cordoro, Kelly M.; Davis, Dawn M.; Feldman, Steven R.; Hanifin, Jon M.; Margolis, David J.; Silverman, Robert A.; Simpson, Eric L.; Williams, Hywel C.; Elmets, Craig A.; Block, Julie; Harrod, Christopher G.; Begolka, Wendy Smith; Sidbury, Robert

2014-01-01

Atopic dermatitis (AD) is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of four sections, treatment of AD with non-pharmacological interventions and pharmacological topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence. PMID:24813302

Gold(I) and Gold(III) Complexes of Cyclic (Alkyl)(amino)carbenes

PubMed Central

2016-01-01

The chemistry of Au(I) complexes with two types of cyclic (alkyl)(amino)carbene (CAAC) ligands has been explored, using the sterically less demanding dimethyl derivative Me2CAAC and the 2-adamantyl ligand AdCAAC. The conversion of (AdCAAC)AuCl into (AdCAAC)AuOH by treatment with KOH is significantly accelerated by the addition of tBuOH. (AdCAAC)AuOH is a convenient starting material for the high-yield syntheses of (AdCAAC)AuX complexes by acid/base and C–H activation reactions (X = OAryl, CF3CO2, N(Tf)2, C2Ph, C6F5, C6HF4, C6H2F3, CH2C(O)C6H4OMe, CH(Ph)C(O)Ph, CH2SO2Ph), while the cationic complexes [(AdCAAC)AuL]+ (L = CO, CNtBu) and (AdCAAC)AuCN were obtained by chloride substitution from (AdCAAC)AuCl. The reactivity toward variously substituted fluoroarenes suggests that (AdCAAC)AuOH is able to react with C–H bonds with pKa values lower than about 31.5. This, together with the spectroscopic data, confirm the somewhat stronger electron-donor properties of CAAC ligands in comparison to imidazolylidene-type N-heterocyclic carbenes (NHCs). In spite of this, the oxidation of Me2CAAC and AdCAAC gold compounds is much less facile. Oxidations proceed with C–Au cleavage by halogens unless light is strictly excluded. The oxidation of (AdCAAC)AuCl with PhICl2 in the dark gives near-quantitative yields of (AdCAAC)AuCl3, while [Au(Me2CAAC)2]Cl leads to trans-[AuCl2(Me2CAAC)2]Cl. In contrast to the chemistry of imidazolylidene-type gold NHC complexes, oxidation products containing Au–Br or Au–I bonds could not be obtained; whereas the reaction with CsBr3 cleaves the Au–C bond to give mixtures of [AdCAAC-Br]+[AuBr2]− and [(AdCAAC-Br)]+ [AuBr4]−, the oxidation of (AdCAAC)AuI with I2 leads to the adduct (AdCAAC)AuI·I2. Irrespective of the steric demands of the CAAC ligands, their gold complexes proved more resistant to oxidation and more prone to halogen cleavage of the Au–C bonds than gold(I) complexes of imidazole-based NHC ligands. PMID:26146436

Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Beck, Michael W.; Derrick, Jeffrey S.; Kerr, Richard A.; Oh, Shin Bi; Cho, Woo Jong; Lee, Shin Jung C.; Ji, Yonghwan; Han, Jiyeon; Tehrani, Zahra Aliakbar; Suh, Nayoung; Kim, Sujeong; Larsen, Scott D.; Kim, Kwang S.; Lee, Joo-Yong; Ruotolo, Brandon T.; Lim, Mi Hee

2016-10-01

The absence of effective therapeutics against Alzheimer's disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal-Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets' reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.

Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer's disease.

PubMed

Beck, Michael W; Derrick, Jeffrey S; Kerr, Richard A; Oh, Shin Bi; Cho, Woo Jong; Lee, Shin Jung C; Ji, Yonghwan; Han, Jiyeon; Tehrani, Zahra Aliakbar; Suh, Nayoung; Kim, Sujeong; Larsen, Scott D; Kim, Kwang S; Lee, Joo-Yong; Ruotolo, Brandon T; Lim, Mi Hee

2016-10-13

The absence of effective therapeutics against Alzheimer's disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal-Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets' reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.

Assessing Clinical Microbiology Practice Guidelines: American Society for Microbiology Ad Hoc Committee on Evidence-Based Laboratory Medicine Practice Guidelines Assessment.

PubMed

Nachamkin, Irving; Kirn, Thomas J; Westblade, Lars F; Humphries, Romney

2017-11-01

As part of the American Society for Microbiology (ASM) Evidence-Based Laboratory Medicine Practice Guidelines Committee of the Professional Practice Committee, an ad hoc committee was formed in 2014 to assess guidelines published by the committee using an assessment tool, Appraisal of Guidelines for Research Evaluation II (AGREE II). The AGREE II assessment helps reviewers determine whether published guidelines are robust, transparent, and clear in presenting practice recommendations in a standardized manner. Identifying strengths and weaknesses of practice guidelines by ad hoc assessments helps with improving future guidelines through the participation of key stakeholders. This minireview describes the development of the ad hoc committee and results from their review of several ASM best practices guidelines and a non-ASM practice guideline from the Emergency Nurses Association. Copyright © 2017 American Society for Microbiology.

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis

PubMed Central

Treutlein, Jens; Streit, Fabian; Juraeva, Dilafruz; Degenhardt, Franziska; Rietschel, Liz; Forstner, Andreas J.; Ridinger, Monika; Dukal, Helene; Foo, Jerome C.; Soyka, Michael; Maier, Wolfgang; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Müller-Myhsok, Bertram; Lucae, Susanne; Ising, Marcus; Stickel, Felix; Berg, Thomas; Roggenbuck, Ulla; Jöckel, Karl-Heinz; Scholz, Henrike; Zimmermann, Ulrich S.; Buch, Stephan; Sommer, Wolfgang H.; Spanagel, Rainer; Brors, Benedikt; Cichon, Sven; Mann, Karl; Kiefer, Falk; Hampe, Jochen; Rosendahl, Jonas; Nöthen, Markus M.; Rietschel, Marcella

2017-01-01

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10−6; pcorrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed. PMID:28714907

Changing attitudes toward smoking and smoking susceptibility through peer crowd targeting: more evidence from a controlled study.

PubMed

Moran, Meghan Bridgid; Sussman, Steve

2015-01-01

Peer crowd identification consistently predicts an adolescent's smoking behavior. As such, several interventions have targeted adolescents and young adults based on their identification with a specific crowd (e.g., Hipsters). This study uses a controlled experimental design to isolate and test the effect of peer crowd targeting in an antismoking ad on antismoking attitudes and smoking susceptibility. Two hundred and thirty-nine adolescents, age 13-15 years, completed a baseline survey and then viewed an antismoking ad targeting one of eight crowds; 1 week later they completed a posttest. Participants were assessed on antismoking attitudes and smoking susceptibility. Adolescents who strongly identified with the crowd targeted by the ad reported stronger antismoking attitudes and lower levels of smoking susceptibility. Those who disidentified with the crowd targeted in the ad exhibited not statistically significant increases in smoking susceptibility and weaker antismoking attitudes at posttest. These findings indicate that targeting youths based on their peer crowd is a useful strategy for antismoking interventions. Additional research should further examine whether youths who disidentify with the targeted crowd in an ad exhibit reactance against the message.

Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.

PubMed

Treutlein, Jens; Frank, Josef; Streit, Fabian; Reinbold, Céline S; Juraeva, Dilafruz; Degenhardt, Franziska; Rietschel, Liz; Witt, Stephanie H; Forstner, Andreas J; Ridinger, Monika; Strohmaier, Jana; Wodarz, Norbert; Dukal, Helene; Foo, Jerome C; Hoffmann, Per; Herms, Stefan; Heilmann-Heimbach, Stefanie; Soyka, Michael; Maier, Wolfgang; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Müller-Myhsok, Bertram; Lucae, Susanne; Ising, Marcus; Stickel, Felix; Berg, Thomas; Roggenbuck, Ulla; Jöckel, Karl-Heinz; Scholz, Henrike; Zimmermann, Ulrich S; Buch, Stephan; Sommer, Wolfgang H; Spanagel, Rainer; Brors, Benedikt; Cichon, Sven; Mann, Karl; Kiefer, Falk; Hampe, Jochen; Rosendahl, Jonas; Nöthen, Markus M; Rietschel, Marcella

2017-07-17

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach ( p uncorrected = 1.2 × 10 -6 ; p corrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed.

Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging.

PubMed

Woodward, Matthew R; Hafeez, Muhammad Ubaid; Qi, Qianya; Riaz, Ahmed; Benedict, Ralph H B; Yan, Li; Szigeti, Kinga

2018-04-19

To explore whether the ability to recognize specific odorant items is differentially affected in aging versus Alzheimer disease (AD); to refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD. Prospective multicenter cross-sectional study with a longitudinal arm. Outpatient memory diagnostic clinics in New York and Texas. Adults aged 65 and older with amnestic mild cognitive impairment (aMCI) and AD and healthy aging (HA) subjects in the comparison group. Participants completed the University of Pennsylvania Smell Identification Test (UPSIT) and neuropsychological testing. AD-associated odorants (AD-10) were selected based on a model of ordinal logistic regression. Age-associated odorants (Age-10) were identified using a linear model. For the 841 participants (234 HA, 192 aMCI, 415 AD), AD-10 was superior to Age-10 in separating HA and AD. AD-10 was associated with a more widespread cognitive deficit across multiple domains, in contrast to Age-10. The disease- and age-associated odorants clustered separately in age and AD. AD-10 predicted conversion from aMCI to AD. Nonoverlapping UPSIT items were identified that were individually associated with age and disease. Despite a modest predictive value of the AD-specific items for conversion to AD, the AD-specific items may be useful in enriching samples to better identify those at risk for AD. Further studies are needed with monomolecular and unilateral stimulation and orthogonal biomarker validation to further refine disease- and age-associated signals. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Novel strategies for Alzheimer's disease treatment: An overview of anti-amyloid beta monoclonal antibodies.

PubMed

Rygiel, Katarzyna

2016-01-01

Alzheimer's disease (AD) is a multifactorial, progressive neurodegenerative disorder with a poor prognosis, and thus, novel therapies for AD are certainly needed in a growing population of elderly patients or asymptomatic individuals, who are at risk for AD, worldwide. It has been established that some AD biomarkers such as amyloid-beta load in the brain, precede the onset of the disease, by approximately 20 years. Therefore, the therapy to prevent or effectively treat AD has to be initiated before the emergence of symptoms. A goal of this review is to present the results of recent clinical trials on monoclonal antibodies against amyloid beta, used for the treatment of AD and also to address some of the current challenges and emerging strategies to prevent AD. In recent trials, a monoclonal antibody, i.e. solanezumab has shown some beneficial cognitive effects among mild AD patients. Ongoing studies with gantenerumab and crenezumab will examine when exactly the AD treatment, aimed at modifying the disease course has to be started. This review was based on Medline database search for trials on passive anti-AD immunotherapy, for which the main timeframe was set from 2012 to 2015.

Structure of a Reptilian Adenovirus Reveals a Phage Tailspike Fold Stabilizing a Vertebrate Virus Capsid.

PubMed

Menéndez-Conejero, Rosa; Nguyen, Thanh H; Singh, Abhimanyu K; Condezo, Gabriela N; Marschang, Rachel E; van Raaij, Mark J; San Martín, Carmen

2017-10-03

Although non-human adenoviruses (AdVs) might offer solutions to problems posed by human AdVs as therapeutic vectors, little is known about their basic biology. In particular, there are no structural studies on the complete virion of any AdV with a non-mammalian host. We combine mass spectrometry, cryo-electron microscopy, and protein crystallography to characterize the composition and structure of a snake AdV (SnAdV-1, Atadenovirus genus). SnAdV-1 particles contain the genus-specific proteins LH3, p32k, and LH2, a previously unrecognized structural component. Remarkably, the cementing protein LH3 has a trimeric β helix fold typical of bacteriophage host attachment proteins. The organization of minor coat proteins differs from that in human AdVs, correlating with higher thermostability in SnAdV-1. These findings add a new piece to the intriguing puzzle of virus evolution, hint at the use of cell entry pathways different from those in human AdVs, and will help development of new, thermostable SnAdV-1-based vectors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phytosterol oxidation products (POP) in foods with added phytosterols and estimation of their daily intake: A literature review

PubMed Central

Knol, Diny; Trautwein, Elke A.

2016-01-01

1 To evaluate the content of phytosterol oxidation products (POP) of foods with added phytosterols, in total 14 studies measuring POP contents of foods with added phytosterols were systematically reviewed. In non‐heated or stored foods, POP contents were low, ranging from (medians) 0.03–3.6 mg/100 g with corresponding oxidation rates of phytosterols (ORP) of 0.03–0.06%. In fat‐based foods with 8% of added free plant sterols (FPS), plant sterol esters (PSE) or plant stanol esters (PAE) pan‐fried at 160–200°C for 5–10 min, median POP contents were 72.0, 38.1, and 4.9 mg/100 g, respectively, with a median ORP of 0.90, 0.48, and 0.06%. Hence resistance to thermal oxidation was in the order of PAE > PSE > FPS. POP formation was highest in enriched butter followed by margarine and rapeseed oil. In margarines with 7.5–10.5% added PSE oven‐heated at 140–200°C for 5–30 min, median POP content was 0.3 mg/100 g. Further heating under same temperature conditions but for 60–120 min markedly increased POP formation to 384.3 mg/100 g. Estimated daily upper POP intake was 47.7 mg/d (equivalent to 0.69 mg/kg BW/d) for foods with added PSE and 78.3 mg/d (equivalent to 1.12 mg/kg BW/d) for foods with added FPS as calculated by multiplying the advised upper daily phytosterol intake of 3 g/d with the 90% quantile values of ORP. In conclusion, heating temperature and time, chemical form of phytosterols added and the food matrix are determinants of POP formation in foods with added phytosterols, leading to an increase in POP contents. Practical applications: Phytosterol oxidation products (POP) are formed in foods containing phytosterols especially when exposed to heat treatment. This review summarising POP contents in foods with added phytosterols in their free and esterified forms reveals that heating temperature and time, the chemical form of phytosterols added and the food matrix itself are determinants of POP formation with heating temperature and time having the biggest impact. The estimated upper daily intakes of POP is 78.3 mg/d for fat‐based products with added free plant sterols and 47.7 mg/d for fat‐based products with added plant sterol esters. Phytosterols in foods are susceptible to oxidation to form phytosterol oxidation products (POP). This review summarizes literature data regarding POP contents of foods with added phytosterols that were exposed to storage and heat treatments. PMID:27812313

Recruiting Young Gay and Bisexual Men for a Human Papillomavirus Vaccination Intervention Through Social Media: The Effects of Advertisement Content.

PubMed

Reiter, Paul L; Katz, Mira L; Bauermeister, Jose A; Shoben, Abigail B; Paskett, Electra D; McRee, Annie-Laurie

2017-06-02

Web-based approaches, specifically social media sites, represent a promising approach for recruiting young gay and bisexual men for research studies. Little is known, however, about how the performance of social media advertisements (ads) used to recruit this population is affected by ad content (ie, image and text). The aim of this study was to evaluate the effects of different images and text included in social media ads used to recruit young gay and bisexual men for the pilot test of a Web-based human papillomavirus (HPV) vaccination intervention. In July and September 2016, we used paid Facebook advertisements to recruit men who were aged 18-25 years, self-identified as gay or bisexual, US resident, and had not received HPV vaccine. A 4x2x2 factorial experiment varied ad image (a single young adult male, a young adult male couple, a group of young adult men, or a young adult male talking to a doctor), content focus (text mentioning HPV or HPV vaccine), and disease framing (text mentioning cancer or a sexually transmitted disease [STD]). Poisson regression determined whether these experimental factors affected ad performance. The recruitment campaign reached a total of 35,646 users who viewed ads for 36,395 times. This resulted in an overall unique click-through rate of 2.01% (717/35,646) and an overall conversion rate of 0.66% (241/36,395). Reach was higher for ads that included an image of a couple (incidence rate ratio, IRR=4.91, 95% CI 2.68-8.97, P<.001) or a group (IRR=2.65, 95% CI 1.08-6.50, P=.03) compared with those that included an image of a single person. Ads that included an image of a couple also had a higher conversion rate (IRR=2.56, 95% CI 1.13-5.77, P=.02) than ads that included an image of a single person. Ads with text mentioning an STD had a higher unique click-through rate compared with ads with text mentioning cancer (IRR=1.34, 95% CI 1.06-1.69, P=.01). The campaign cost a total of US $413.72 and resulted in 150 eligible and enrolled individuals (US $2.76 per enrolled participant). Facebook ads are a convenient and cost-efficient strategy for reaching and recruiting young gay and bisexual men for a Web-based HPV vaccination intervention. To help optimize ad performance among this population, researchers should consider the importance of the text and image included in the social media recruitment ads. ©Paul L Reiter, Mira L Katz, Jose A Bauermeister, Abigail B Shoben, Electra D Paskett, Annie-Laurie McRee. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 02.06.2017.

A stable partitioned FSI algorithm for rigid bodies and incompressible flow. Part I: Model problem analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Banks, J. W.; Henshaw, W. D.; Schwendeman, D. W.

A stable partitioned algorithm is developed for fluid-structure interaction (FSI) problems involving viscous incompressible flow and rigid bodies. This added-mass partitioned (AMP) algorithm remains stable, without sub-iterations, for light and even zero mass rigid bodies when added-mass and viscous added-damping effects are large. The scheme is based on a generalized Robin interface condition for the fluid pressure that includes terms involving the linear acceleration and angular acceleration of the rigid body. Added mass effects are handled in the Robin condition by inclusion of a boundary integral term that depends on the pressure. Added-damping effects due to the viscous shear forcesmore » on the body are treated by inclusion of added-damping tensors that are derived through a linearization of the integrals defining the force and torque. Added-damping effects may be important at low Reynolds number, or, for example, in the case of a rotating cylinder or rotating sphere when the rotational moments of inertia are small. In this second part of a two-part series, the general formulation of the AMP scheme is presented including the form of the AMP interface conditions and added-damping tensors for general geometries. A fully second-order accurate implementation of the AMP scheme is developed in two dimensions based on a fractional-step method for the incompressible Navier-Stokes equations using finite difference methods and overlapping grids to handle the moving geometry. Here, the numerical scheme is verified on a number of difficult benchmark problems.« less

Analysis of spontaneous MEG activity in mild cognitive impairment and Alzheimer's disease using spectral entropies and statistical complexity measures

NASA Astrophysics Data System (ADS)

Bruña, Ricardo; Poza, Jesús; Gómez, Carlos; García, María; Fernández, Alberto; Hornero, Roberto

2012-06-01

Alzheimer's disease (AD) is the most common cause of dementia. Over the last few years, a considerable effort has been devoted to exploring new biomarkers. Nevertheless, a better understanding of brain dynamics is still required to optimize therapeutic strategies. In this regard, the characterization of mild cognitive impairment (MCI) is crucial, due to the high conversion rate from MCI to AD. However, only a few studies have focused on the analysis of magnetoencephalographic (MEG) rhythms to characterize AD and MCI. In this study, we assess the ability of several parameters derived from information theory to describe spontaneous MEG activity from 36 AD patients, 18 MCI subjects and 26 controls. Three entropies (Shannon, Tsallis and Rényi entropies), one disequilibrium measure (based on Euclidean distance ED) and three statistical complexities (based on Lopez Ruiz-Mancini-Calbet complexity LMC) were used to estimate the irregularity and statistical complexity of MEG activity. Statistically significant differences between AD patients and controls were obtained with all parameters (p < 0.01). In addition, statistically significant differences between MCI subjects and controls were achieved by ED and LMC (p < 0.05). In order to assess the diagnostic ability of the parameters, a linear discriminant analysis with a leave-one-out cross-validation procedure was applied. The accuracies reached 83.9% and 65.9% to discriminate AD and MCI subjects from controls, respectively. Our findings suggest that MCI subjects exhibit an intermediate pattern of abnormalities between normal aging and AD. Furthermore, the proposed parameters provide a new description of brain dynamics in AD and MCI.

Translational research in genomics of Alzheimer's disease: a review of current practice and future perspectives.

PubMed

Mihaescu, Raluca; Detmar, Symone B; Cornel, Martina C; van der Flier, Wiesje M; Heutink, Peter; Hol, Elly M; Rikkert, Marcel G M Olde; van Duijn, Cornelia M; Janssens, A Cecile J W

2010-01-01

Alzheimer's disease (AD) is the most prevalent form of dementia and the number of cases is expected to increase exponentially worldwide. Three highly penetrant genes (AbetaPP, PSEN1, and PSEN2) explain only a small number of AD cases with a Mendelian transmission pattern. Many genes have been analyzed for association with non-Mendelian AD, but the only consistently replicated finding is APOE. At present, possibilities for prevention, early detection, and treatment of the disease are limited. Predictive and diagnostic genetic testing is available only in Mendelian forms of AD. Currently, APOE genotyping is not considered clinically useful for screening, presymptomatic testing, or clinical diagnosis of non-Mendelian AD. However, clinical management of the disease is expected to benefit from the rapid pace of discoveries in the genomics of AD. Following a recently developed framework for the continuum of translation research that is needed to move genetic discoveries to health applications, this paper reviews recent genetic discoveries as well as translational research on genomic applications in the prevention, early detection, and treatment of AD. The four phases of translation research include: 1) translation of basic genomics research into a potential health care application; 2) evaluation of the application for the development of evidence-based guidelines; 3) evaluation of the implementation and use of the application in health care practice; and 4) evaluation of the achieved population health impact. Most research on genome-based applications in AD is still in the first phase of the translational research framework, which means that further research is still needed before their implementation can be considered.

A stable partitioned FSI algorithm for rigid bodies and incompressible flow. Part I: Model problem analysis

DOE PAGES

Banks, J. W.; Henshaw, W. D.; Schwendeman, D. W.; ...

2017-01-20

A stable partitioned algorithm is developed for fluid-structure interaction (FSI) problems involving viscous incompressible flow and rigid bodies. This added-mass partitioned (AMP) algorithm remains stable, without sub-iterations, for light and even zero mass rigid bodies when added-mass and viscous added-damping effects are large. The scheme is based on a generalized Robin interface condition for the fluid pressure that includes terms involving the linear acceleration and angular acceleration of the rigid body. Added mass effects are handled in the Robin condition by inclusion of a boundary integral term that depends on the pressure. Added-damping effects due to the viscous shear forcesmore » on the body are treated by inclusion of added-damping tensors that are derived through a linearization of the integrals defining the force and torque. Added-damping effects may be important at low Reynolds number, or, for example, in the case of a rotating cylinder or rotating sphere when the rotational moments of inertia are small. In this second part of a two-part series, the general formulation of the AMP scheme is presented including the form of the AMP interface conditions and added-damping tensors for general geometries. A fully second-order accurate implementation of the AMP scheme is developed in two dimensions based on a fractional-step method for the incompressible Navier-Stokes equations using finite difference methods and overlapping grids to handle the moving geometry. Here, the numerical scheme is verified on a number of difficult benchmark problems.« less

A combination of supplements may reduce the risk of Alzheimer's disease in elderly Japanese with normal cognition.

PubMed

Bun, Shogyoku; Ikejima, Chiaki; Kida, Jiro; Yoshimura, Atsuko; Lebowitz, Adam Jon; Kakuma, Tatsuyuki; Asada, Takashi

2015-01-01

A number of studies have examined the effect of a single supplement against Alzheimer's disease (AD) with conflicting results. Taking into account the complex and multifactorial nature of AD pathogenesis, multiple supplements may be more effective. Physical activity is another prospect against AD. An open-label intervention study was conducted to explore a potential protective effect of multiple supplements and physical activity. Their interaction was also examined. Participants were community-dwelling volunteers aged 65 or older as of May 2001 in a rural area of Japan. Among 918 cognitively normal participants included in the analyses, 171 took capsules daily for three years that contained n-3 polyunsaturated fatty acid, Ginkgo biloba leaf dry extracts, and lycopene. Two hundred and forty one participants joined the two-year exercise intervention that included a community center-based and a home-based exercise program. One-hundred and forty eight participated in both interventions. A standardized neuropsychological battery was administered at baseline in 2001, the first follow-up in 2004-2005, and the second in 2008-2009. The primary outcome was AD diagnosis at follow-ups. A complementary log-log model was used for survival analysis. A total of 76 participants were diagnosed with AD during follow-up periods. Higher adherence to supplementation intervention was associated with lower AD incidence in both unadjusted and adjusted models. Exercise intervention was also associated with lower AD incidence in the unadjusted model, but not in the adjusted model. We hypothesized that the combination of supplements acted in a complementary and synergistic fashion to bring significant effects against AD occurrence.

Immune Recognition of Gene Transfer Vectors: Focus on Adenovirus as a Paradigm

PubMed Central

Aldhamen, Yasser Ali; Seregin, Sergey S.; Amalfitano, Andrea

2011-01-01

Recombinant Adenovirus (Ad) based vectors have been utilized extensively as a gene transfer platform in multiple pre-clinical and clinical applications. These applications are numerous, and inclusive of both gene therapy and vaccine based approaches to human or animal diseases. The widespread utilization of these vectors in both animal models, as well as numerous human clinical trials (Ad-based vectors surpass all other gene transfer vectors relative to numbers of patients treated, as well as number of clinical trials overall), has shed light on how this virus vector interacts with both the innate and adaptive immune systems. The ability to generate and administer large amounts of this vector likely contributes not only to their ability to allow for highly efficient gene transfer, but also their elicitation of host immune responses to the vector and/or the transgene the vector expresses in vivo. These facts, coupled with utilization of several models that allow for full detection of these responses has predicted several observations made in human trials, an important point as lack of similar capabilities by other vector systems may prevent detection of such responses until only after human trials are initiated. Finally, induction of innate or adaptive immune responses by Ad vectors may be detrimental in one setting (i.e., gene therapy) and be entirely beneficial in another (i.e., prophylactic or therapeutic vaccine based applications). Herein, we review the current understanding of innate and adaptive immune responses to Ad vectors, as well some recent advances that attempt to capitalize on this understanding so as to further broaden the safe and efficient use of Ad-based gene transfer therapies in general. PMID:22566830

EXADS - EXPERT SYSTEM FOR AUTOMATED DESIGN SYNTHESIS

NASA Technical Reports Server (NTRS)

Rogers, J. L.

1994-01-01

The expert system called EXADS was developed to aid users of the Automated Design Synthesis (ADS) general purpose optimization program. Because of the general purpose nature of ADS, it is difficult for a nonexpert to select the best choice of strategy, optimizer, and one-dimensional search options from the one hundred or so combinations that are available. EXADS aids engineers in determining the best combination based on their knowledge of the problem and the expert knowledge previously stored by experts who developed ADS. EXADS is a customized application of the AESOP artificial intelligence program (the general version of AESOP is available separately from COSMIC. The ADS program is also available from COSMIC.) The expert system consists of two main components. The knowledge base contains about 200 rules and is divided into three categories: constrained, unconstrained, and constrained treated as unconstrained. The EXADS inference engine is rule-based and makes decisions about a particular situation using hypotheses (potential solutions), rules, and answers to questions drawn from the rule base. EXADS is backward-chaining, that is, it works from hypothesis to facts. The rule base was compiled from sources such as literature searches, ADS documentation, and engineer surveys. EXADS will accept answers such as yes, no, maybe, likely, and don't know, or a certainty factor ranging from 0 to 10. When any hypothesis reaches a confidence level of 90% or more, it is deemed as the best choice and displayed to the user. If no hypothesis is confirmed, the user can examine explanations of why the hypotheses failed to reach the 90% level. The IBM PC version of EXADS is written in IQ-LISP for execution under DOS 2.0 or higher with a central memory requirement of approximately 512K of 8 bit bytes. This program was developed in 1986.

Increased efficacy of an adenovirus-vectored foot-and-mouth disease capsid subunit vaccine expressing nonstructural protein 2B is associated with a specific T cell response

USDA-ARS?s Scientific Manuscript database

We previously demonstrated that an adenovirus-based FMDV serotype A24 subunit vaccine, Ad5-A24, expressed under the control of a cytomegalovirus promoter (CMV) can protect swine and bovines against homologous challenge, but swine vaccinated with an Ad5-vectored FMDV O1 Campos vaccine, Ad5-O1Campos (...

Reputation-Based Internet Protocol Security: A Multilayer Security Framework for Mobile Ad Hoc Networks

DTIC Science & Technology

2010-09-01

secure ad-hoc networks of mobile sensors deployed in a hostile environment . These sensors are normally small 86 and resource...Communications Magazine, 51, 2008. 45. Kumar, S.A. “Classification and Review of Security Schemes in Mobile Comput- ing”. Wireless Sensor Network , 2010... Networks ”. Wireless /Mobile Network Security , 2008. 85. Xiao, Y. “Accountability for Wireless LANs, Ad Hoc Networks , and Wireless

Performance Analysis of Hierarchical Group Key Management Integrated with Adaptive Intrusion Detection in Mobile ad hoc Networks

DTIC Science & Technology

2016-04-05

applications in wireless networks such as military battlefields, emergency response, mobile commerce , online gaming, and collaborative work are based on the...www.elsevier.com/locate/peva Performance analysis of hierarchical group key management integrated with adaptive intrusion detection in mobile ad hoc...Accepted 19 September 2010 Available online 26 September 2010 Keywords: Mobile ad hoc networks Intrusion detection Group communication systems Group

Meta-Analysis of a Continuous Outcome Combining Individual Patient Data and Aggregate Data: A Method Based on Simulated Individual Patient Data

ERIC Educational Resources Information Center

Yamaguchi, Yusuke; Sakamoto, Wataru; Goto, Masashi; Staessen, Jan A.; Wang, Jiguang; Gueyffier, Francois; Riley, Richard D.

2014-01-01

When some trials provide individual patient data (IPD) and the others provide only aggregate data (AD), meta-analysis methods for combining IPD and AD are required. We propose a method that reconstructs the missing IPD for AD trials by a Bayesian sampling procedure and then applies an IPD meta-analysis model to the mixture of simulated IPD and…

Relationship between Added Sugars Consumption and Chronic Disease Risk Factors: Current Understanding.

PubMed

Rippe, James M; Angelopoulos, Theodore J

2016-11-04

Added sugars are a controversial and hotly debated topic. Consumption of added sugars has been implicated in increased risk of a variety of chronic diseases including obesity, cardiovascular disease, diabetes and non-alcoholic fatty liver disease (NAFLD) as well as cognitive decline and even some cancers. Support for these putative associations has been challenged, however, on a variety of fronts. The purpose of the current review is to summarize high impact evidence including systematic reviews, meta-analyses, and randomized controlled trials (RCTs), in an attempt to provide an overview of current evidence related to added sugars and health considerations. This paper is an extension of a symposium held at the Experimental Biology 2015 conference entitled "Sweeteners and Health: Current Understandings, Controversies, Recent Research Findings and Directions for Future Research". We conclude based on high quality evidence from randomized controlled trials (RCT), systematic reviews and meta-analyses of cohort studies that singling out added sugars as unique culprits for metabolically based diseases such as obesity, diabetes and cardiovascular disease appears inconsistent with modern, high quality evidence and is very unlikely to yield health benefits. While it is prudent to consume added sugars in moderation, the reduction of these components of the diet without other reductions of caloric sources seems unlikely to achieve any meaningful benefit.

Relationship between Added Sugars Consumption and Chronic Disease Risk Factors: Current Understanding

PubMed Central

Rippe, James M.; Angelopoulos, Theodore J.

2016-01-01

Added sugars are a controversial and hotly debated topic. Consumption of added sugars has been implicated in increased risk of a variety of chronic diseases including obesity, cardiovascular disease, diabetes and non-alcoholic fatty liver disease (NAFLD) as well as cognitive decline and even some cancers. Support for these putative associations has been challenged, however, on a variety of fronts. The purpose of the current review is to summarize high impact evidence including systematic reviews, meta-analyses, and randomized controlled trials (RCTs), in an attempt to provide an overview of current evidence related to added sugars and health considerations. This paper is an extension of a symposium held at the Experimental Biology 2015 conference entitled “Sweeteners and Health: Current Understandings, Controversies, Recent Research Findings and Directions for Future Research”. We conclude based on high quality evidence from randomized controlled trials (RCT), systematic reviews and meta-analyses of cohort studies that singling out added sugars as unique culprits for metabolically based diseases such as obesity, diabetes and cardiovascular disease appears inconsistent with modern, high quality evidence and is very unlikely to yield health benefits. While it is prudent to consume added sugars in moderation, the reduction of these components of the diet without other reductions of caloric sources seems unlikely to achieve any meaningful benefit. PMID:27827899

Removal of polycyclic synthetic musks and antineoplastic drugs in ozonated wastewater: Quantitation based on the data of differential spectroscopy.

PubMed

Li, Wei; Nanaboina, Venkateswarlu; Chen, Fang; Korshin, Gregory V

2016-03-05

This study examined the degradation behavior of polycyclic musks (PMs) and antineoplastic drugs (ADs) and the absorbance spectra of effluent organic matter (EfOM) in municipal wastewater by ozone. Specific ozone doses used in the experiments ranged from 0 to 1mg O3/mg dissolved organic matter (DOC). The examined PMs included galaxolide, tonalide, celestolide, traseolide and phantolide. ADs included busulfan, chlorambucil, cyclophosphamide, dacarbazine, flutamide, ifosfamide, tamoxifen and methotrexate. Strong monotonic albeit nonlinear correlations were found to exist between relative changes of EfOM absorbance at 254 nm (i.e. ΔA254/A(0)254) and the degradation of the selected PMs and ADs. This result was interpreted based on the concept of the simultaneous oxidation of EfOM and, on the other hand, PMs and ADs. This interpretation showed that PMs were degraded primarily via OH radical attack, with tonalide and phantolide being less reactive compared with the other PMs. ADs such as cyclophosphamide, ifosfamide and busulfan were also determined to undergo oxidation by OH radicals. Comparison of the behavior of the radical probe para-chlorobenzoic acid and the examined ADs and PMs allowed evaluating corresponding reaction rate constants for reactions between these species and OH radicals. Copyright © 2015 Elsevier B.V. All rights reserved.

CFD Based Added Mass Prediction in Cruise Condition of Underwater Vehicle Dynamic

NASA Astrophysics Data System (ADS)

Agoes Moelyadi, Mochammad; Bambang Riswandi, Bagus

2018-04-01

One of the unsteady flow behavior on the hydrodynamic characteristics of underwater vehicle is the presence of added mass. In cruising conditions, the underwater vehicle may require the addition of speed or experience the disturbance in the form of unsteady flow so that cause the hydrodynamic interaction between the surface of the vehicle with the surrounding fluid. This leads to the rise of local velocity of flow and the great changes of hydrodynamic forces which are very influential on the stability of the underwater vehicle. One of the result is an additional force called added mass. It is very useful parameter to control underwater vehicle dynamic.This paper reports the research on the added mass coefficient of underwater vehicles obtained through the Computational Fluid Dynmaic (CFD) simulation method using CFX software. Added mass coefficient is calculated by performing an unsteady simulation or known as transient simulation. Computational simulations are based on the Reynold Average Navier- Stokes (RANS) equation solution. The simulated vehicle moves forward and backward according to the sinus function, with a frequency of 0.25 Hz, a 2 m amplitude, a cruising depth of 10 m below sea level, and Vcruise 1.54 m / s (Re = 9.000.000). Simulation result data includes velocity contour, variation of force and acceleration to frequency, and added mass coefficient.

Clinical utility of FDG-PET for the differential diagnosis among the main forms of dementia.

PubMed

Nestor, Peter J; Altomare, Daniele; Festari, Cristina; Drzezga, Alexander; Rivolta, Jasmine; Walker, Zuzana; Bouwman, Femke; Orini, Stefania; Law, Ian; Agosta, Federica; Arbizu, Javier; Boccardi, Marina; Nobili, Flavio; Frisoni, Giovanni Battista

2018-05-07

To assess the clinical utility of FDG-PET as a diagnostic aid for differentiating Alzheimer's disease (AD; both typical and atypical forms), dementia with Lewy bodies (DLB), frontotemporal lobar degeneration (FTLD), vascular dementia (VaD) and non-degenerative pseudodementia. A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted on six different diagnostic scenarios using the Delphi method. The level of empirical study evidence for the use of FDG-PET was considered good for the discrimination of DLB and AD; fair for discriminating FTLD from AD; poor for atypical AD; and lacking for discriminating DLB from FTLD, AD from VaD, and for pseudodementia. Delphi voting led to consensus in all scenarios within two iterations. Panellists supported the use of FDG-PET for all PICOs-including those where study evidence was poor or lacking-based on its negative predictive value and on the assistance it provides when typical patterns of hypometabolism for a given diagnosis are observed. Although there is an overall lack of evidence on which to base strong recommendations, it was generally concluded that FDG-PET has a diagnostic role in all scenarios. Prospective studies targeting diagnostically uncertain patients for assessing the added value of FDG-PET would be highly desirable.

Anticholinergic Exposure and Risk of Pneumonia in Persons with Alzheimer's Disease: A Nested Case-Control Study.

PubMed

Lampela, Pasi; Tolppanen, Anna-Maija; Tanskanen, Antti; Tiihonen, Jari; Hartikainen, Sirpa; Taipale, Heidi

2017-01-01

Risk of pneumonia is increased in persons with Alzheimer's disease (AD). In some studies, anticholinergic drugs (AC) have been associated with an increased pneumonia risk. We analyzed the risk of pneumonia associated with ACs in persons with AD. We performed a nested case-control study using register-based data from a Finnish nationwide MEDALZ cohort including all community-dwelling persons diagnosed with AD during 2005-2011. Cases were identified based on pneumonia diagnoses (n = 12,442) from hospital discharge and causes of death registers. Up to two controls without pneumonia were matched based on time since AD diagnoses, age, and gender for each case; AC use was measured using Anticholinergic Drug Scale. Use of AC was associated with an increased risk of pneumonia (adjusted odds ratio (OR) 1.36, 95% confidence interval (CI) 1.29-1.43). However, there was no increased pneumonia risk in persons using level 3 ACs. Incident use was associated with higher risk of pneumonia (OR 2.68, 95% CI 2.15-3.34) than prevalent use (OR 1.48, 95% CI 1.40-1.57). Among persons using cholinesterase inhibitors (AChEIs), risk of pneumonia was increased in persons using also ACs (OR 1.53, 95% CI 1.41-1.66). ACs were associated with an increased risk of pneumonia in persons with AD, especially at the time of initiation of these drugs. AC use was associated with increased pneumonia risk also in persons using AChEIs. This risk should be carefully considered when treating AD patients.

Heart diseases and long-term risk of dementia and Alzheimer's disease: a population-based CAIDE study.

PubMed

Rusanen, Minna; Kivipelto, Miia; Levälahti, Esko; Laatikainen, Tiina; Tuomilehto, Jaakko; Soininen, Hilkka; Ngandu, Tiia

2014-01-01

Many cardiovascular risk factors are shown to increase the risk of dementia and Alzheimer's disease (AD), but the impact of heart disease on later development of dementia is still unclear. The aim of the study was to investigate the long-term risk of dementia and Alzheimer's disease (AD) related to midlife and late-life atrial fibrillation (AF), heart failure (HF), and coronary artery disease (CAD) in a population-based study with a follow-up of over 25 years. Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study includes 2000 participants who were randomly selected from four separate, population-based samples originally studied in midlife (1972, 1977, 1982, or 1987). Re-examinations were carried out in 1998 and 2005-2008. Altogether 1,510 (75.5%) persons participated in at least one re-examination, and 127 (8.4%) persons were diagnosed with dementia (of which 102 had AD). AF in late-life was an independent risk factor for dementia (HR 2.61, 95% CI 1.05-6.47; p = 0.039) and AD (HR 2.54, 95% CI 1.04-6.16; p = 0.040) in the fully adjusted analyses. The association was even stronger among the apolipoprotein E (APOE) ε4 non-carriers. Late-life HF, but not CAD, tended to increase the risks as well. Heart diseases diagnosed at midlife did not increase the risk of later dementia and AD. Late-life heart diseases increase the subsequent risk of dementia and AD. Prevention and effective treatment of heart diseases may be important also from the perspective of brain health and cognitive functioning.

Effect of iron salt type and dosing mode on Fenton-based pretreatment of rice straw for enzymatic hydrolysis.

PubMed

Gan, Yu-Yan; Zhou, Si-Li; Dai, Xiao; Wu, Han; Xiong, Zi-Yao; Qin, Yuan-Hang; Ma, Jiayu; Yang, Li; Wu, Zai-Kun; Wang, Tie-Lin; Wang, Wei-Guo; Wang, Cun-Wen

2018-06-15

Fenton-based processes with four different iron salts in two different dosing modes were used to pretreat rice straw (RS) samples to increase their enzymatic digestibility. The composition analysis shows that the RS sample pretreated by the dosing mode of iron salt adding into H 2 O 2 has a much lower hemicellulose content than that pretreated by the dosing mode of H 2 O 2 adding into iron salt, and the RS sample pretreated by the chloride salt-based Fenton process has a much lower lignin content and a slightly lower hemicellulose content than that pretreated by the sulphate salt-based Fenton process. The higher concentration of reducing sugar observed on the RS sample with lower lignin and hemicellulose contents justifies that the Fenton-based process could enhance the enzymic hydrolysis of RS by removing hemicellulose and lignin and increasing its accessibility to cellulase. FeCl 3 ·6H 2 O adding into H 2 O 2 is the most efficient Fenton-based process for RS pretreatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Association between Diabetes and Risk of Aortic Dissection: A Case-Control Study in a Chinese Population.

PubMed

He, Xingwei; Liu, Xintian; Liu, Wanjun; Wang, Bei; Liu, Yujian; Li, Zhuxi; Wang, Tao; Tan, Rong; Gao, Bo; Zeng, Hesong

2015-01-01

It is well-recognized that diabetes represents a powerful independent risk factor for cardiovascular diseases. However, very few studies have investigated the relationship between diabetes and risk of aortic dissection (AD). The aim of this case-control study was to evaluate the association between diabetes and risk of AD in Chinese population. A hospital-based case-control study, consisting of 2160 AD patients and 4320 controls, was conducted in a Chinese population. Demographic, clinical characteristics and risk factors were collected. Diabetes rate of patients with overall AD, Stanford type A AD and type B AD group was compared with that of corresponding matched control groups. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for relationship between diabetes and AD risk. The prevalence of diabetes was lower in AD cases than that of control subjects, whether it is the overall AD, type A AD or type B AD group (4.7% vs. 10.0%, 2.9% vs. 8.8%, 5.9% vs. 10.9%, all P<0.001). Furthermore, in multivariate model, diabetes was found to be associated with lower AD risk, which not only applies to the overall AD (OR = 0.2, 95%CI: 0.15-0.26), but also type A AD (OR = 0.12, 95% CI: 0.07-0.20) and type B AD (OR = 0.25, 95%CI: 0.18-0.33). We observed the paradoxical inverse relationship between DM and risk of AD in the Chinese population. These results suggest diabetes may play a protective role in the development of AD. However, further studies are needed to enrich related evidence, especially with regard to underlying mechanisms for these trends.

Prediction of population with Alzheimer's disease in the European Union using a system dynamics model.

PubMed

Tomaskova, Hana; Kuhnova, Jitka; Cimler, Richard; Dolezal, Ondrej; Kuca, Kamil

2016-01-01

Alzheimer's disease (AD) is a slowly progressing neurodegenerative brain disease with irreversible brain effects; it is the most common cause of dementia. With increasing age, the probability of suffering from AD increases. In this research, population growth of the European Union (EU) until the year 2080 and the number of patients with AD are modeled. The aim of this research is to predict the spread of AD in the EU population until year 2080 using a computer simulation. For the simulation of the EU population and the occurrence of AD in this population, a system dynamics modeling approach has been used. System dynamics is a useful and effective method for the investigation of complex social systems. Over the past decades, its applicability has been demonstrated in a wide variety of applications. In this research, this method has been used to investigate the growth of the EU population and predict the number of patients with AD. The model has been calibrated on the population prediction data created by Eurostat. Based on data from Eurostat, the EU population until year 2080 has been modeled. In 2013, the population of the EU was 508 million and the number of patients with AD was 7.5 million. Based on the prediction, in 2040, the population of the EU will be 524 million and the number of patients with AD will be 13.1 million. By the year 2080, the EU population will be 520 million and the number of patients with AD will be 13.7 million. System dynamics modeling approach has been used for the prediction of the number of patients with AD in the EU population till the year 2080. These results can be used to determine the economic burden of the treatment of these patients. With different input data, the simulation can be used also for the different regions as well as for different noncontagious disease predictions.

Earth horizon modeling and application to static Earth sensors on TRMM spacecraft

NASA Technical Reports Server (NTRS)

Keat, J.; Challa, M.; Tracewell, D.; Galal, K.

1995-01-01

Data from Earth sensor assemblies (ESA's) often are used in the attitude determination (AD) for both spinning and Earth-pointing spacecraft. The ESA's on previous such spacecraft for which the ground-based AD operation was performed by the Flight Dynamics Division (FDD) used the Earth scanning method. AD on such spacecraft requires a model of the shape of the Earth disk as seen from the spacecraft. AD accuracy requirements often are too severe to permit Earth oblateness to be ignored when modeling disk shape. Section 2 of this paper reexamines and extends the methods for Earth disk shape modeling employed in AD work at FDD for the past decade. A new formulation, based on a more convenient Earth flatness parameter, is introduced, and the geometric concepts are examined in detail. It is shown that the Earth disk can be approximated as an ellipse in AD computations. Algorithms for introducing Earth oblateness into the AD process for spacecraft carrying scanning ESA's have been developed at FDD and implemented into the support systems. The Tropical Rainfall Measurement Mission (TRMM) will be the first spacecraft with AD operation performed at FDD that uses a different type of ESA - namely, a static one - containing four fixed detectors D(sub i) (i = 1 to 4). Section 3 of this paper considers the effect of Earth oblateness on AD accuracy for TRMM. This effect ideally will not induce AD errors on TRMM when data from all four D(sub i) are present. When data from only two or three D(sub i) are available, however, a spherical Earth approximation can introduce errors of 0.05 to 0.30 deg on TRMM. These oblateness-induced errors are eliminated by a new algorithm that uses the results of Section 2 to model the Earth disk as an ellipse.

Performance Analysis of Automatic Dependent Surveillance-Broadcast (ADS-B) and Breakdown of Anomalies

NASA Astrophysics Data System (ADS)

Tabassum, Asma

This thesis work analyzes the performance of Automatic Dependent Surveillance-Broadcast (ADS-B) data received from Grand Forks International Airport, detects anomalies in the data and quantifies the associated potential risk. This work also assesses severity associated anomalous data in Detect and Avoid (DAA) for Unmanned Aircraft System (UAS). The received data were raw and archived in GDL-90 format. A python module is developed to parse the raw data into readable data in a .csv file. The anomaly detection algorithm is based on Federal Aviation Administration's (FAA) ADS-B performance assessment report. An extensive study is carried out on two main types of anomalies, namely dropouts and altitude deviations. A dropout is considered when the update rate exceeds three seconds. Dropouts are of different durations and have a different level of risk depending on how much time ADS-B is unavailable as the surveillance system. Altitude deviation refers to the deviation between barometric and geometric altitude. Deviation ranges from 25 feet to 600 feet have been observed. As of now, barometric altitude has been used for separation and surveillance while geometric altitude can be used in cases where barometric altitude is not available. Many UAS might not have both sensors installed on board due to size and weight constrains. There might be a chance of misinterpretation of vertical separation specially while flying in National Airspace (NAS) if the ownship UAS and intruder manned aircraft use two different altitude sources for separation standard. The characteristics and agreement between two different altitudes is investigated with a regression based approach. Multiple risk matrices are established based on the severity of the DAA well clear. ADS-B is called the Backbone of FAA Next Generation Air Transportation System, NextGen. NextGen is the series of inter-linked programs, systems, and policies that implement advanced technologies and capabilities. ADS-B utilizes the Satellite based Global Positioning System (GPS) technology to provide the pilot and the Air Traffic Control (ATC) with more information which enables an efficient navigation of aircraft in increasingly congested airspace. FAA mandated all aircraft, both manned and unmanned, be equipped with ADS-B out by the year 2020 to fly within most controlled airspace. As a fundamental component of NextGen it is crucial to understand the behavior and potential risk with ADS-B Systems.

Sex and the development of Alzheimer’s disease

PubMed Central

Pike, Christian J.

2016-01-01

Men and women exhibit differences in the development and progression of Alzheimer’s disease (AD). The factors underlying the sex differences in AD are not well understood. This review emphasizes the contributions of sex steroid hormones to the relationship between sex and AD. In women, events that decrease lifetime exposure to estrogens are generally associated with increased AD risk, whereas estrogen-based hormone therapy administered near the time of menopause may reduce AD risk. In men, estrogens do not exhibit age-related reduction and are not significantly associated with AD risk. Rather, normal age-related depletions of testosterone in plasma and brain predict enhanced vulnerability to AD. Both estrogens and androgens exert numerous protective actions in the adult brain that increase neural functioning and resilience as well as specifically attenuate multiple aspects of AD-related neuropathology. Aging diminishes the activational effects of sex hormones in sex-specific manners, which is hypothesized to contribute to the relationship between aging and AD. Sex steroid hormones may also drive sex differences in AD through their organizational effects during developmental sexual differentiation of the brain. Specifically, sex hormone actions during early development may confer inherent vulnerability of the female brain to development of AD in advanced age. The combined effects of organizational and activational effects of sex steroids yield distinct sex differences in AD pathogenesis, a significant variable that must be more rigorously considered in future research. PMID:27870425

A ECG Signal Gathering and Displaying System Based on AVR

NASA Astrophysics Data System (ADS)

Ning, Li; Ruilan, Zhang; Jian, Liu; Xiaochen, Wang; Shuying, Chen; Zhuolin, Lang

2017-12-01

This article introduces a kind of system which is based on the AVR to acquire the data of ECG. Such system using the A/D function of ATmega8 chip and the lattice graph LCD to design ECG heart acquisition satisfies the demands above. This design gives a composition of hardware and programming of software about the system in detail which has mainly realized the real-time gathering, the amplifier, the filter, the A/D transformation and the LCD display. Since the AVR includes A/D transformation function and support embedded C language programming, it reduces the peripheral circuit, further more it also decreases the time to design and debug this system.

A Double Selection Approach to Achieve Specific Expression of Toxin Genes for Ovarian Cancer Gene Therapy

DTIC Science & Technology

2005-11-01

biological properties. CAV-1 is known to cause allergic two knobs may in fact be distinct based on our uveitis, called the ’blue eye syndrome ’ and rarely...system - first steps towards gene therapy of Alport syndrome . Gene Ther 3(1), 2 1-7. Hemminki, A., and Alvarez, R. D. 2002. Adenoviruses in oncology: a...Ad-IX- Ad-IX-imRFPI or Ad-IX-tdimer2(12) (10000 viral particles/ tdimer2(12) with plX modifications, and wild-type El/E3 cell) were added to the

Aerial photography based census of Adélie Penguin and its application in CH4 and N2O budget estimation in Victoria Land, Antarctic.

PubMed

He, Hong; Cheng, Xiao; Li, Xianglan; Zhu, Renbin; Hui, Fengming; Wu, Wenhui; Zhao, Tiancheng; Kang, Jing; Tang, Jianwu

2017-10-11

Penguin guano provides favorable conditions for production and emission of greenhouse gases (GHGs). Many studies have been conducted to determine the GHG fluxes from penguin colonies, however, at regional scale, there is still no accurate estimation of total GHG emissions. We used object-based image analysis (OBIA) method to estimate the Adélie penguin (Pygoscelis adeliae) population based on aerial photography data. A model was developed to estimate total GHG emission potential from Adélie penguin colonies during breeding seasons in 1983 and 2012, respectively. Results indicated that OBIA method was effective for extracting penguin information from aerial photographs. There were 17,120 and 21,183 Adélie penguin breeding pairs on Inexpressible Island in 1983 and 2012, respectively, with overall accuracy of the estimation of 76.8%. The main reasons for the increase in Adélie penguin populations were attributed to increase in temperature, sea ice and phytoplankton. The average estimated CH 4 and N 2 O emissions tended to be increasing during the period from 1983 to 2012 and CH 4 was the main GHG emitted from penguin colonies. Total global warming potential (GWP) of CH 4 and N 2 O emissions was 5303 kg CO 2 -eq in 1983 and 6561 kg CO 2 -eq in 2012, respectively.

Characterization of complexity in the electroencephalograph activity of Alzheimer's disease based on fuzzy entropy.

PubMed

Cao, Yuzhen; Cai, Lihui; Wang, Jiang; Wang, Ruofan; Yu, Haitao; Cao, Yibin; Liu, Jing

2015-08-01

In this paper, experimental neurophysiologic recording and statistical analysis are combined to investigate the nonlinear characteristic and the cognitive function of the brain. Fuzzy approximate entropy and fuzzy sample entropy are applied to characterize the model-based simulated series and electroencephalograph (EEG) series of Alzheimer's disease (AD). The effectiveness and advantages of these two kinds of fuzzy entropy are first verified through the simulated EEG series generated by the alpha rhythm model, including stronger relative consistency and robustness. Furthermore, in order to detect the abnormality of irregularity and chaotic behavior in the AD brain, the complexity features based on these two fuzzy entropies are extracted in the delta, theta, alpha, and beta bands. It is demonstrated that, due to the introduction of fuzzy set theory, the fuzzy entropies could better distinguish EEG signals of AD from that of the normal than the approximate entropy and sample entropy. Moreover, the entropy values of AD are significantly decreased in the alpha band, particularly in the temporal brain region, such as electrode T3 and T4. In addition, fuzzy sample entropy could achieve higher group differences in different brain regions and higher average classification accuracy of 88.1% by support vector machine classifier. The obtained results prove that fuzzy sample entropy may be a powerful tool to characterize the complexity abnormalities of AD, which could be helpful in further understanding of the disease.

Characterization of complexity in the electroencephalograph activity of Alzheimer's disease based on fuzzy entropy

NASA Astrophysics Data System (ADS)

Cao, Yuzhen; Cai, Lihui; Wang, Jiang; Wang, Ruofan; Yu, Haitao; Cao, Yibin; Liu, Jing

2015-08-01

In this paper, experimental neurophysiologic recording and statistical analysis are combined to investigate the nonlinear characteristic and the cognitive function of the brain. Fuzzy approximate entropy and fuzzy sample entropy are applied to characterize the model-based simulated series and electroencephalograph (EEG) series of Alzheimer's disease (AD). The effectiveness and advantages of these two kinds of fuzzy entropy are first verified through the simulated EEG series generated by the alpha rhythm model, including stronger relative consistency and robustness. Furthermore, in order to detect the abnormality of irregularity and chaotic behavior in the AD brain, the complexity features based on these two fuzzy entropies are extracted in the delta, theta, alpha, and beta bands. It is demonstrated that, due to the introduction of fuzzy set theory, the fuzzy entropies could better distinguish EEG signals of AD from that of the normal than the approximate entropy and sample entropy. Moreover, the entropy values of AD are significantly decreased in the alpha band, particularly in the temporal brain region, such as electrode T3 and T4. In addition, fuzzy sample entropy could achieve higher group differences in different brain regions and higher average classification accuracy of 88.1% by support vector machine classifier. The obtained results prove that fuzzy sample entropy may be a powerful tool to characterize the complexity abnormalities of AD, which could be helpful in further understanding of the disease.

Developing Systems Engineering Experience Accelerator (SEEA) Prototype and Roadmap -- Increment 4

DTIC Science & Technology

2017-08-08

of an acquisition program, two categories of new capabilities were added to the UAV experience. Based on a student project at Stevens Institute of...program for a new unmanned aerial vehicle (UAV) system. It was based on the concept of the learners assuming this role shortly after preliminary...University curriculum for systems engineers. First, several new capabilities have been added. These include a trade study for additional technical

Adding Postal Follow-Up to a Web-Based Survey of Primary Care and Gastroenterology Clinic Physician Chiefs Improved Response Rates but not Response Quality or Representativeness.

PubMed

Partin, Melissa R; Powell, Adam A; Burgess, Diana J; Haggstrom, David A; Gravely, Amy A; Halek, Krysten; Bangerter, Ann; Shaukat, Aasma; Nelson, David B

2015-09-01

This study assessed whether postal follow-up to a web-based physician survey improves response rates, response quality, and representativeness. We recruited primary care and gastroenterology chiefs at 125 Veterans Affairs medical facilities to complete a 10-min web-based survey on colorectal cancer screening and diagnostic practices in 2010. We compared response rates, response errors, and representativeness in the primary care and gastroenterology samples before and after adding postal follow-up. Adding postal follow-up increased response rates by 20-25 percentage points; markedly greater increases than predicted from a third e-mail reminder. In the gastroenterology sample, the mean number of response errors made by web responders (0.25) was significantly smaller than the mean number made by postal responders (2.18), and web responders provided significantly longer responses to open-ended questions. There were no significant differences in these outcomes in the primary care sample. Adequate representativeness was achieved before postal follow-up in both samples, as indicated by the lack of significant differences between web responders and the recruitment population on facility characteristics. We conclude adding postal follow-up to this web-based physician leader survey improved response rates but not response quality or representativeness. © The Author(s) 2013.

Reducing the Conflict Factors Strategies in Question Answering System

NASA Astrophysics Data System (ADS)

Suwarningsih, W.; Purwarianti, A.; Supriana, I.

2017-03-01

A rule-based system is prone to conflict as new knowledge every time will emerge and indirectly must sign in to the knowledge base that is used by the system. A conflict occurred between the rules in the knowledge base can lead to the errors of reasoning or reasoning circulation. Therefore, when added, the new rules will lead to conflict with other rules, and the only rules that really can be added to the knowledge base. From these conditions, this paper aims to propose a conflict resolution strategy for a medical debriefing system by analyzing scenarios based upon the runtime to improve the efficiency and reliability of systems.

Experimental investigation of the influence of nanoparticles on water-based mud

NASA Astrophysics Data System (ADS)

Dhiman, Paritosh; Cheng, Yaoze; Zhang, Yin; Patil, Shirish

2018-03-01

This study has investigated the influence of nanoparticles including nanoparticle concentration, size, and type on water-based mud (WBM) properties including rheology, filtration, and lubricity through experimental tests, while the influence of temperature and aging on these properties have been investigated. It has been found that adding SiO2 nanoparticles increase the plastic viscosity and decrease the yield points and gel strengths with the increase of nanoparticle concentration. At fixed 0.5 wt%, the plastic viscosity decreases with the increase of TiO2 nanoparticle size, but the influence of TiO2 nanoparticle size on yield points and gel strengths is not monotonous. In general, adding negative charged SiO2 nanoparticles reduce the yield points and gel strengths, while adding positively charged TiO2, Al2O3, and Fe3O4 nanoparticles increase yield points and gel strengths. Adding lower concentrations (< 0.05 wt%) of SiO2 nanoparticles improved mud filtration and lubricity properties, but higher concentrations are adverse to these properties and adding 0.5 wt% TiO2, Al2O3 and Fe3O4 nanoparticles impaired these properties. Besides, it is found that there is no consistent influence of aging on mud properties and adding nanoparticles cannot improve aging resistance of mud. Although adding nanoparticles can significantly affect WBM properties, their influences are not consistency, depending on the integrated impact of the nanoparticle properties, such as surface electrical property, specific surface area, concentration, and size.

Midlife personality and risk of Alzheimer disease and distress: a 38-year follow-up.

PubMed

Johansson, Lena; Guo, Xinxin; Duberstein, Paul R; Hällström, Tore; Waern, Margda; Ostling, Svante; Skoog, Ingmar

2014-10-21

To study the association between midlife neuroticism and extraversion and development of late-life dementia and long-standing distress in a sample of women followed for 38 years. A population-based sample of 800 women, aged 38 to 54 years, was examined in 1968, with subsequent examinations in 1974, 1980, 1992, 2000, and 2005. Neuroticism and extraversion were assessed using the Eysenck Personality Inventory at baseline. Distress was measured according to a standardized question at each study wave. Dementia was diagnosed according to DSM-III-R criteria based on information from neuropsychiatric examinations, informant interviews, hospital records, and registry data. During the 38-year follow-up, 153 women developed dementia; Alzheimer disease (AD) dementia was diagnosed in 104 of these. A higher degree of neuroticism in midlife was associated with increased risk of AD dementia and long-standing distress over 38 years. The association between neuroticism and AD dementia diminished after adjusting for long-standing distress. Extraversion was associated with a lower degree of long-standing distress, but had no impact on AD dementia. When the 2 personality dimensions were combined, high neuroticism/low extraversion showed the highest risk of AD dementia. Our study suggests that midlife neuroticism is associated with increased risk of AD dementia, and that distress mediates this association. The results have clinical implications because a group of women at risk of AD dementia is identified. © 2014 American Academy of Neurology.

Functional brain networks in Alzheimer's disease: EEG analysis based on limited penetrable visibility graph and phase space method

NASA Astrophysics Data System (ADS)

Wang, Jiang; Yang, Chen; Wang, Ruofan; Yu, Haitao; Cao, Yibin; Liu, Jing

2016-10-01

In this paper, EEG series are applied to construct functional connections with the correlation between different regions in order to investigate the nonlinear characteristic and the cognitive function of the brain with Alzheimer's disease (AD). First, limited penetrable visibility graph (LPVG) and phase space method map single EEG series into networks, and investigate the underlying chaotic system dynamics of AD brain. Topological properties of the networks are extracted, such as average path length and clustering coefficient. It is found that the network topology of AD in several local brain regions are different from that of the control group with no statistically significant difference existing all over the brain. Furthermore, in order to detect the abnormality of AD brain as a whole, functional connections among different brain regions are reconstructed based on similarity of clustering coefficient sequence (CCSS) of EEG series in the four frequency bands (delta, theta, alpha, and beta), which exhibit obvious small-world properties. Graph analysis demonstrates that for both methodologies, the functional connections between regions of AD brain decrease, particularly in the alpha frequency band. AD causes the graph index complexity of the functional network decreased, the small-world properties weakened, and the vulnerability increased. The obtained results show that the brain functional network constructed by LPVG and phase space method might be more effective to distinguish AD from the normal control than the analysis of single series, which is helpful for revealing the underlying pathological mechanism of the disease.

Voxel-based morphometry in Alzheimers disease and mild cognitive impairment: Systematic review of studies addressing the frontal lobe

PubMed Central

Ribeiro, Luís Gustavo; Busatto, Geraldo

2016-01-01

ABSTRACT Voxel-based morphometry (VBM) is a useful approach for investigating neurostructural brain changes in dementia. We systematically reviewed VBM studies of Alzheimer's disease (AD) and mild cognitive impairment (MCI), specifically focusing on grey matter (GM) atrophy in the frontal lobe. Methods: Two searches were performed on the Pubmed database. A set of exclusion criteria was applied to ensure the selection of only VBM studies that directly investigated GM volume abnormalities in AD and/or MCI patients compared to cognitively normal controls. Results: From a total of 46 selected articles, 35 VBM studies reported GM volume reductions in the frontal lobe. The frontal subregions, where most of the volume reductions were reported, included the inferior, superior and middle frontal gyri, as well as the anterior cingulate gyrus. We also found studies in which reduced frontal GM was detected in MCI patients who converted to AD. In a minority of studies, correlations between frontal GM volumes and behavioural changes or cognitive deficits in AD patients were investigated, with variable findings. Conclusion: Results of VBM studies indicate that the frontal lobe should be regarded as an important brain area when investigating GM volume deficits in association with AD. Frontal GM loss might not be a feature specific to late AD only. Future VBM studies involving large AD samples are warranted to further investigate correlations between frontal volume deficits and both cognitive impairment and neuropsychiatric symptoms. PMID:29213441

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PubMed Central

Shi, Zhao-feng; Song, Tie-bing; Xie, Juan; Yan, Yi-quan

2017-01-01

Background Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. Objective The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. Methods Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. Results The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. Conclusion We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future. PMID:28713436

Early detection of AD using cortical thickness measurements

NASA Astrophysics Data System (ADS)

Spjuth, M.; Gravesen, F.; Eskildsen, S. F.; Østergaard, L. R.

2007-03-01

Alzheimer's disease (AD) is a neurodegenerative disorder that causes cortical atrophy and impaired cognitive functions. The diagnosis is difficult to make and is often made over a longer period of time using a combination of neuropsychological tests, and structural and functional imaging. Due to the impact of early intervention the challenge of distinguishing early AD from normal ageing has received increasing attention. This study uses cortical thickness measurements to characterize the atrophy in nine mild AD patients (mean MMSE-score 23.3 (std: 2.6)) compared to five healthy middle-aged subjects. A fully automated method based on deformable models is used for delineation of the inner and outer boundaries of the cerebral cortex from Magnetic Resonance Images. This allows observer independent high-resolution quantification of the cortical thickness. The cortex analysis facilitates detection of alterations throughout the entire cortical mantle. To perform inter-subject thickness comparison in which the spatial information is retained, a feature-based registration algorithm is developed which uses local cortical curvature, normal vector, and a distance measure. A comparison of the two study groups reveals that the lateral side of the hemispheres shows diffuse thinner areas in the mild AD group but especially the medial side shows a pronounced thinner area which can be explained by early limbic changes in AD. For classification principal component analysis is applied to reduce the high number of thickness measurements (>200,000) into fewer features. All mild AD and healthy middle-aged subjects are classified correctly (sensitivity and specificity 100%).

An experimental study of the effects of electronic cigarette warnings on young adult nonsmokers' perceptions and behavioral intentions.

PubMed

Mays, Darren; Smith, Clayton; Johnson, Andrea C; Tercyak, Kenneth P; Niaura, Raymond S

2016-01-01

Electronic cigarette ("e-cigarette") manufacturers use warning labels on their advertising that vary widely in content and the U.S. Food and Drug Administration has issued a warning label requirement for e-cigarettes. There is limited data on the effects of these warnings on e-cigarette perceptions and other potential predictors of future tobacco use behavior in populations of interest to inform future regulatory requirements. This study examined the effects of e-cigarette warnings on perceptions of e-cigarettes and cigarettes and other cognitive precursors to tobacco use among young adult non-smokers. Non-smoking young adults ages 18 to 30 years (n = 436) were recruited through an internet-based crowdsourcing platform for an online experiment. Participants completed pre-exposure measures of demographics, tobacco use, and other relevant constructs and were randomized to view 1 of 9 e-cigarette stimuli in a 3 (Ad/Warning condition: Ad Only, Ad with Warning, Warning Only) x 3 (E-cigarette brand: Blu, MarkTen, Vuse) design. After viewing e-cigarette stimuli, participants reported perceptions of e-cigarettes and behavioral intentions to use e-cigarettes. Participants in the Ad Only and Ad with Warning conditions also completed a heat-mapping task assessing aspects of the ads that captured their attention. Then, participants were randomized to view cigarette ads from 1 of 3 major cigarette brands and reported perceptions of cigarettes and intentions to smoke cigarettes. Participants in the Warning Only condition reported significantly greater perceived harm and addictiveness of e-cigarettes and thoughts about not using e-cigarettes than the Ad Only and Ad with Warning conditions (p's < .05). The Ad Only and Ad with Warning conditions did not differ on these outcomes. Participants in the Warning Only condition also reported the harms of e-cigarettes were closer to those of cigarettes than the Ad Only condition (p < .05), but neither differed from the Ad with Warning condition. Visual inspection of heat-mapping task data indicate warnings drew few participants' attention. There were no significant differences across study conditions on perceptions of cigarettes or intentions to smoke. Text-based warning messages influenced young non-smokers' perceptions in a way that may dissuade e-cigarette use, but warnings appearing on advertisements had little impact.

Comparative Analysis of the Magnitude, Quality, Phenotype and Protective Capacity of SIV Gag-Specific CD8+ T Cells Following Human-, Simian- and Chimpanzee-Derived Recombinant Adenoviral Vector Immunisation

PubMed Central

Quinn, Kylie M.; Costa, Andreia Da; Yamamoto, Ayako; Berry, Dana; Lindsay, Ross W.B.; Darrah, Patricia A.; Wang, Lingshu; Cheng, Cheng; Kong, Wing-Pui; Gall, Jason G.D.; Nicosia, Alfredo; Folgori, Antonella; Colloca, Stefano; Cortese, Riccardo; Gostick, Emma; Price, David A.; Gomez, Carmen E.; Esteban, Mariano; Wyatt, Linda S.; Moss, Bernard; Morgan, Cecilia; Roederer, Mario; Bailer, Robert T.; Nabel, Gary J.; Koup, Richard A.; Seder, Robert A.

2013-01-01

Recombinant adenoviral vectors (rAds) are the most potent recombinant vaccines for eliciting CD8+ T cell-mediated immunity in humans; however, prior exposure from natural adenoviral infection can decrease such responses. Here we show low seroreactivity in humans against simian- (sAd11, sAd16), or chimpanzee-derived (chAd3, chAd63) compared to human-derived (rAd5, rAd28, rAd35) vectors across multiple geographic regions. We then compared the magnitude, quality, phenotype and protective capacity of CD8+ T cell responses in mice vaccinated with rAds encoding SIV Gag. Using a dose range (1 × 107 to 109 PU), we defined a hierarchy among rAd vectors based on the magnitude and protective capacity of CD8+ T cell responses, from most to least as: rAd5 and chAd3, rAd28 and sAd11, chAd63, sAd16, and rAd35. Selection of rAd vector or dose could modulate the proportion and/or frequency of IFNγ+TNFα+IL-2+ and KLRG1+CD127- CD8+ T cells, but strikingly ~30–80% of memory CD8+ T cells co-expressed CD127 and KLRG1. To further optimise CD8+ T cell responses, we assessed rAds as part of prime-boost regimens. Mice primed with rAds and boosted with NYVAC generated Gag-specific responses that approached ~60% of total CD8+ T cells at peak. Alternatively, priming with DNA or rAd28 and boosting with rAd5 or chAd3 induced robust and equivalent CD8+ T cell responses compared to prime or boost alone. Collectively, these data provide the immunologic basis for using specific rAd vectors alone or as part of prime-boost regimens to induce CD8+ T cells for rapid effector function or robust long-term memory, respectively. PMID:23390298

Using an Alzheimer Disease Polygenic Risk Score to Predict Memory Decline in Black and White Americans Over 14 Years of Follow-up.

PubMed

Marden, Jessica R; Mayeda, Elizabeth R; Walter, Stefan; Vivot, Alexandre; Tchetgen Tchetgen, Eric J; Kawachi, Ichiro; Glymour, M Maria

2016-01-01

Evidence on whether genetic predictors of Alzheimer disease (AD) also predict memory decline is inconsistent, and limited data are available for African ancestry populations. For 8253 non-Hispanic white (NHW) and non-Hispanic black (NHB) Health and Retirement Study participants with memory scores measured 1 to 8 times between 1998 and 2012 (average baseline age=62), we calculated weighted polygenic risk scores [AD Genetic Risk Score (AD-GRS)] using the top 22 AD-associated loci, and an alternative score excluding apolipoprotein E (APOE) (AD-GRSexAPOE). We used generalized linear models with AD-GRS-by-age and AD-GRS-by-age interactions (age centered at 70) to predict memory decline. Average NHB decline was 26% faster than NHW decline (P<0.001). Among NHW, 10% higher AD-GRS predicted faster memory decline (linear β=-0.058 unit decrease over 10 y; 95% confidence interval,-0.074 to -0.043). AD-GRSexAPOE also predicted faster decline for NHW, although less strongly. Among NHB, AD-GRS predicted faster memory decline (linear β=-0.050; 95% confidence interval, -0.106 to 0.006), but AD-GRSexAPOE did not. Our nonsignificant estimate among NHB may reflect insufficient statistical power or a misspecified AD-GRS among NHB as an overwhelming majority of genome-wide association studies are conducted in NHW. A polygenic score based on previously identified AD loci predicts memory loss in US blacks and whites.

The Role of Security Assistance in the Andean Initiative

DTIC Science & Technology

1992-01-01

acid is added to the kerosene mixture, forming cocaine sulfate. The kerosene is removed, more alkaline is added and cocaine paste forms in the pit...Kerosene is added to the paste, forming cocaine crystals. The crystals are washed in alcohol and dissolved in acid , filtered, and dried. The dried...substance is cocaine base, which is further refined, with either, acetone, and acid , into cocaine hydrochloride.$ These operations are conducted in the

Automated Driving System Architecture to Ensure Safe Delegation of Driving Authority

NASA Astrophysics Data System (ADS)

YUN, Sunkil; NISHIMURA, Hidekazu

2016-09-01

In this paper, the architecture of an automated driving system (ADS) is proposed to ensure safe delegation of driving authority between the ADS and a driver. Limitations of the ADS functions may activate delegation of driving authority to a driver. However, it leads to severe consequences in emergency situations where a driver may be drowsy or distracted. To address these issues, first, the concept model for the ADS in the situation for delegation of driving authority is described taking the driver's behaviour and state into account. Second, the behaviour / state of a driver and functional flow / state of ADS and the interactions between them are modelled to understand the context where the ADS requests to delegate the driving authority to a driver. Finally, the proposed architecture of the ADS is verified under the simulations based on the emergency braking scenarios. In the verification process using simulation, we have derived the necessary condition for safe delegation of driving authority is that the ADS should assist s driver even after delegating driving authority to a driver who has not enough capability to regain control of the driving task.

Assessing the TARES as an ethical model for antismoking ads.

PubMed

Lee, Seow Ting; Cheng, I-Huei

2010-01-01

This study examines the ethical dimensions of public health communication, with a focus on antismoking public service announcements (PSAs). The content analysis of 826 television ads from the U.S. Centers for Disease Control and Prevention's (CDC) Media Campaign Resource Center is an empirical testing of Baker and Martinson's (2001) TARES Test that directly examines persuasive messages for truthfulness, authenticity, respect, equity, and social responsibility. In general, the antismoking ads score highly on ethicality. There are significant relationships between ethicality and message attributes (thematic frame, emotion appeal, source, and target audience). Ads that portrayed smoking as damaging to health and socially unacceptable score lower in ethicality than ads that focus on tobacco industry manipulation, addiction, dangers of secondhand smoke, and cessation. Emotion appeals of anger and sadness are associated with higher ethicality than shame and humor appeals. Ads targeting teen/youth audiences score lower on ethicality than ads targeting adult and general audiences. There are significant differences in ethicality based on source; ads produced by the CDC rate higher in ethicality than other sources. Theoretical implications and practical recommendations are discussed.

Interpreting labels of abuse-deterrent opioid analgesics.

PubMed

Webster, Lynn R

To provide an overview of available abuse-deterrent opioids (ADOs) and the labeling text that describes abuse-deterrent (AD) properties. A nonsystematic review of ADO literature and regulatory documents guiding their development. A critical assessment and discussion of common routes of opioid abuse, AD methods and properties, US Food and Drug Administration (FDA) study requirements to achieve AD labeling, and brief guide to understanding AD labels. The FDA has issued guidance as incentive and direction to industry to develop ADOs as one component of a multi-pronged public-health strategy to combat opioid abuse and misuse. The guidance describes separate categories of premarket and postmarket studies and makes recommendations for claims that may be made based on study findings. Ten ADOs have FDA-approved labeling attesting to AD properties. Available formulations that fail to conform to FDA guidance in study and labeling recommendations cannot be considered ADO. Formulations with AD properties are expected to reduce risk compared to the same agents without AD properties but cannot prevent all abuse and adverse clinical outcomes.

Probability of Alzheimer's disease in breast cancer survivors based on gray-matter structural network efficiency.

PubMed

Kesler, Shelli R; Rao, Vikram; Ray, William J; Rao, Arvind

2017-01-01

Breast cancer chemotherapy is associated with accelerated aging and potentially increased risk for Alzheimer's disease (AD). We calculated the probability of AD diagnosis from brain network and demographic and genetic data obtained from 47 female AD converters and 47 matched healthy controls. We then applied this algorithm to data from 78 breast cancer survivors. The classifier discriminated between AD and healthy controls with 86% accuracy ( P  < .0001). Chemotherapy-treated breast cancer survivors demonstrated significantly higher probability of AD compared to healthy controls ( P  < .0001) and chemotherapy-naïve survivors ( P  = .007), even after stratifying for apolipoprotein e4 genotype. Chemotherapy-naïve survivors also showed higher AD probability compared to healthy controls ( P  = .014). Chemotherapy-treated breast cancer survivors who have a particular profile of brain structure may have a higher risk for AD, especially those who are older and have lower cognitive reserve.

Epigenetic Drug Repositioning for Alzheimer's Disease Based on Epigenetic Targets in Human Interactome.

PubMed

Chatterjee, Paulami; Roy, Debjani; Rathi, Nitin

2018-01-01

Epigenetics has emerged as an important field in drug discovery. Alzheimer's disease (AD), the leading neurodegenerative disorder throughout the world, is shown to have an epigenetic basis. Currently, there are very few effective epigenetic drugs available for AD. In this work, for the first time we have proposed 14 AD repositioning epigenetic drugs and identified their targets from extensive human interactome. Interacting partners of the AD epigenetic proteins were identified from the extensive human interactome to construct Epigenetic Protein-Protein Interaction Network (EP-PPIN). Epigenetic Drug-Target Network (EP-DTN) was constructed with the drugs associated with the proteins of EP-PPIN. Regulation of non-coding RNAs associated with the target proteins of these drugs was also studied. AD related target proteins, epigenetic targets, enriched pathways, and functional categories of the proposed repositioning drugs were also studied. The proposed 14 AD epigenetic repositioning drugs have overlapping targets and miRs with known AD epigenetic targets and miRs. Furthermore, several shared functional categories and enriched pathways were obtained for these drugs with FDA approved epigenetic drugs and known AD drugs. The findings of our work might provide insight into future AD epigenetic-therapeutics.

Revealing Alzheimer's disease genes spectrum in the whole-genome by machine learning.

PubMed

Huang, Xiaoyan; Liu, Hankui; Li, Xinming; Guan, Liping; Li, Jiankang; Tellier, Laurent Christian Asker M; Yang, Huanming; Wang, Jian; Zhang, Jianguo

2018-01-10

Alzheimer's disease (AD) is an important, progressive neurodegenerative disease, with a complex genetic architecture. A key goal of biomedical research is to seek out disease risk genes, and to elucidate the function of these risk genes in the development of disease. For this purpose, expanding the AD-associated gene set is necessary. In past research, the prediction methods for AD related genes has been limited in their exploration of the target genome regions. We here present a genome-wide method for AD candidate genes predictions. We present a machine learning approach (SVM), based upon integrating gene expression data with human brain-specific gene network data, to discover the full spectrum of AD genes across the whole genome. We classified AD candidate genes with an accuracy and the area under the receiver operating characteristic (ROC) curve of 84.56% and 94%. Our approach provides a supplement for the spectrum of AD-associated genes extracted from more than 20,000 genes in a genome wide scale. In this study, we have elucidated the whole-genome spectrum of AD, using a machine learning approach. Through this method, we expect for the candidate gene catalogue to provide a more comprehensive annotation of AD for researchers.

At the interface of sensory and motor dysfunctions and Alzheimer's disease.

PubMed

Albers, Mark W; Gilmore, Grover C; Kaye, Jeffrey; Murphy, Claire; Wingfield, Arthur; Bennett, David A; Boxer, Adam L; Buchman, Aron S; Cruickshanks, Karen J; Devanand, Davangere P; Duffy, Charles J; Gall, Christine M; Gates, George A; Granholm, Ann-Charlotte; Hensch, Takao; Holtzer, Roee; Hyman, Bradley T; Lin, Frank R; McKee, Ann C; Morris, John C; Petersen, Ronald C; Silbert, Lisa C; Struble, Robert G; Trojanowski, John Q; Verghese, Joe; Wilson, Donald A; Xu, Shunbin; Zhang, Li I

2015-01-01

Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer's disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age-related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled "Sensory and Motor Dysfunctions in Aging and AD." The scientific sessions of the workshop focused on age-related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory-motor deficits in AD may enhance patient function as AD progresses. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Early Statin Use and the Progression of Alzheimer Disease: A Total Population-Based Case-Control Study.

PubMed

Lin, Feng-Cheng; Chuang, Yun-Shiuan; Hsieh, Hui-Min; Lee, Tzu-Chi; Chiu, Kuei-Fen; Liu, Ching-Kuan; Wu, Ming-Tsang

2015-11-01

The protective effect of statin on Alzheimer disease (AD) is still controversial, probably due to the debate about when to start the use of statin and the lack of any large-scale randomized evidence that actually supports the hypothesis. The purpose of this study was to examine the protective effect of early statin use on mild-to-moderate AD in the total Taiwanese population.This was a total population-based case-control study, using the total population of Taiwanese citizens seen in general medical practice; therefore, the findings can be applied to the general population. The study patients were those with newly diagnosed dementia (ICD-9 290.x) and prescribed any acetylcholinesterase inhibitors (AChEI) from the Taiwan National Health Insurance dataset in 1997 to 2008. The newly diagnosed eligible mild-to-moderate AD patients were traced from the dates of their index dates, which was defined as the first day to receive any AChEI treatment, back to 1 year (exposure period) to categorize them into AD with early statin use and without early statin use. Early statin use was defined as patients using statin before AChEI treatment. Alzheimer disease patients with early statin use were those receiving any statin treatment during the exposure period. Then, we used propensity-score-matched strategy to match these 2 groups as 1:1. The matched study patients were followed-up from their index dates. The primary outcome was the discontinuation of AChEI treatment, indicating AD progression.There were 719 mild-to-moderate AD-paired patients with early statin use and without early statin use for analyses. Alzheimer disease progression was statistically lower in AD patients with early statin use than those without (P = 0.00054). After adjusting for other covariates, mild-to-moderate AD patients with early stain use exhibited a 0.85-risk (95% CI = 0.76-0.95, P = 0.0066) to have AD progression than those without.Early statin use was significantly associated with a reduction in AD progression in mild-to-moderate AD patients. The future randomized trial studies can confirm our findings.

Progressive aphasia secondary to Alzheimer disease pathology: A clinicopathologic and MRI study

PubMed Central

Josephs, Keith A.; Whitwell, Jennifer L.; Duffy, Joseph R.; Vanvoorst, Wendy A.; Strand, Edyth A.; Hu, William T.; Boeve, Bradley F.; Graff-Radford, Neill R.; Parisi, Joseph E.; Knopman, David S.; Dickson, Dennis W.; Jack, Clifford R.; Petersen, Ronald C.

2009-01-01

Background The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive-inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD). Objective To compare clinicopathological and MRI features of subjects with progressive aphasia and AD pathology, to subjects with aphasia and FTLD-U pathology, and subjects with typical AD. Methods We identified 5 subjects with aphasia and AD pathology and 5 with aphasia and FTLD-U pathology with an MRI from a total of 216 aphasia subjects. Ten subjects with typical AD clinical features and AD pathology were also identified. All subjects with AD pathology underwent pathological re-analysis with TDP-43 immunohistochemistry. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the aphasia cases with AD pathology, aphasia cases with FTLD-U, and typical AD cases with AD pathology, compared to a normal control group. Results All aphasic subjects had fluent speech output. However, those with AD pathology had better processing speed than those with FTLD-U pathology. Immunohistochemistry with TDP-43 antibodies was negative. VBM revealed grey matter atrophy predominantly in the temporoparietal cortices with notable sparing of the hippocampus in the aphasia with AD subjects. In comparison, the aphasic subjects with FTLD-U showed sparing of the parietal lobe. Typical AD subjects showed temporoparietal and hippocampal atrophy. Conclusions A temporoparietal pattern of atrophy on MRI in patients with progressive fluent aphasia and relatively preserved processing speed is suggestive of underlying AD pathology rather than FTLD-U. PMID:18166704

Financial and health literacy predict incident AD dementia and AD pathology

PubMed Central

Yu, Lei; Wilson, Robert S.; Schneider, Julie A.; Bennett, David A.; Boyle, Patricia A.

2017-01-01

Background Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. Objective We test the hypothesis that domain specific literacy is associated with AD dementia and AD pathology after controlling for cognition. Methods Participants were community based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined post-mortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. Results All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p<0.001), and the association persisted after controlling for cognition (Hazard Ratio=1.50, p=0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β=0.07, p=0.035). Conclusion Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition. PMID:28157101

Are restrictive guidelines for added sugars science based?

PubMed

Erickson, Jennifer; Slavin, Joanne

2015-12-12

Added sugar regulations and recommendations have been proposed by policy makers around the world. With no universal definition, limited access to added sugar values in food products and no analytical difference from intrinsic sugars, added sugar recommendations present a unique challenge. Average added sugar intake by American adults is approximately 13% of total energy intake, and recommendations have been made as low 5% of total energy intake. In addition to public health recommendations, the Food and Drug Administration has proposed the inclusion of added sugar data to the Nutrition and Supplemental Facts Panel. The adoption of such regulations would have implications for both consumers as well as the food industry. There are certainly advantages to including added sugar data to the Nutrition Facts Panel; however, consumer research does not consistently show the addition of this information to improve consumer knowledge. With excess calorie consumption resulting in weight gain and increased risk of obesity and obesity related co-morbidities, added sugar consumption should be minimized. However, there is currently no evidence stating that added sugar is more harmful than excess calories from any other food source. The addition of restrictive added sugar recommendations may not be the most effective intervention in the treatment and prevention of obesity and other health concerns.

Magnetic resonance imaging biomarkers for the early diagnosis of Alzheimer's disease: a machine learning approach.

PubMed

Salvatore, Christian; Cerasa, Antonio; Battista, Petronilla; Gilardi, Maria C; Quattrone, Aldo; Castiglioni, Isabella

2015-01-01

Determination of sensitive and specific markers of very early AD progression is intended to aid researchers and clinicians to develop new treatments and monitor their effectiveness, as well as to lessen the time and cost of clinical trials. Magnetic Resonance (MR)-related biomarkers have been recently identified by the use of machine learning methods for the in vivo differential diagnosis of AD. However, the vast majority of neuroimaging papers investigating this topic are focused on the difference between AD and patients with mild cognitive impairment (MCI), not considering the impact of MCI patients who will (MCIc) or not convert (MCInc) to AD. Morphological T1-weighted MRIs of 137 AD, 76 MCIc, 134 MCInc, and 162 healthy controls (CN) selected from the Alzheimer's disease neuroimaging initiative (ADNI) cohort, were used by an optimized machine learning algorithm. Voxels influencing the classification between these AD-related pre-clinical phases involved hippocampus, entorhinal cortex, basal ganglia, gyrus rectus, precuneus, and cerebellum, all critical regions known to be strongly involved in the pathophysiological mechanisms of AD. Classification accuracy was 76% AD vs. CN, 72% MCIc vs. CN, 66% MCIc vs. MCInc (nested 20-fold cross validation). Our data encourage the application of computer-based diagnosis in clinical practice of AD opening new prospective in the early management of AD patients.

Total, Added, and Free Sugars: Are Restrictive Guidelines Science-Based or Achievable?

PubMed Central

Erickson, Jennifer; Slavin, Joanne

2015-01-01

Sugar consumption, especially added sugars, is under attack. Various government and health authorities have suggested new sugar recommendations and guidelines as low as 5% of total calories from free sugars. Definitions for total sugars, free sugars, and added sugars are not standardized, nor are there accepted nutrient databases for this information. Our objective was to measure total sugars and added sugars in sample meal plans created by the United States Department of Agriculture (USDA) and the Academy of Nutrition and Dietetics (AND). Utilizing the Nutrition Data System for Research (NDSR) nutritional database, results found that plans created by the USDA and AND averaged 5.1% and 3.1% calories from added sugar, 8.7% and 3.1% from free sugar, and 23.3% and 21.1% as total sugars respectively. Compliance with proposed added sugar recommendations would require strict dietary compliance and may not be sustainable for many Americans. Without an accepted definition and equation for calculating added sugar, added sugar recommendations are arbitrary and may reduce intakes of nutrient-rich, recommended foods, such as yogurt, whole grains, and tart fruits including cranberries, cherries, and grapefruit. Added sugars are one part of excess calorie intake; however, compliance with low added sugar recommendations may not be achievable for the general public. PMID:25884659

Total, added, and free sugars: are restrictive guidelines science-based or achievable?

PubMed

Erickson, Jennifer; Slavin, Joanne

2015-04-15

Sugar consumption, especially added sugars, is under attack. Various government and health authorities have suggested new sugar recommendations and guidelines as low as 5% of total calories from free sugars. Definitions for total sugars, free sugars, and added sugars are not standardized, nor are there accepted nutrient databases for this information. Our objective was to measure total sugars and added sugars in sample meal plans created by the United States Department of Agriculture (USDA) and the Academy of Nutrition and Dietetics (AND). Utilizing the Nutrition Data System for Research (NDSR) nutritional database, results found that plans created by the USDA and AND averaged 5.1% and 3.1% calories from added sugar, 8.7% and 3.1% from free sugar, and 23.3% and 21.1% as total sugars respectively. Compliance with proposed added sugar recommendations would require strict dietary compliance and may not be sustainable for many Americans. Without an accepted definition and equation for calculating added sugar, added sugar recommendations are arbitrary and may reduce intakes of nutrient-rich, recommended foods, such as yogurt, whole grains, and tart fruits including cranberries, cherries, and grapefruit. Added sugars are one part of excess calorie intake; however, compliance with low added sugar recommendations may not be achievable for the general public.

Introducing ADS Labs

NASA Astrophysics Data System (ADS)

Accomazzi, Alberto; Henneken, E.; Grant, C. S.; Kurtz, M. J.; Di Milia, G.; Luker, J.; Thompson, D. M.; Bohlen, E.; Murray, S. S.

2011-05-01

ADS Labs is a platform that ADS is introducing in order to test and receive feedback from the community on new technologies and prototype services. Currently, ADS Labs features a new interface for abstract searches, faceted filtering of results, visualization of co-authorship networks, article-level recommendations, and a full-text search service. The streamlined abstract search interface provides a simple, one-box search with options for ranking results based on a paper relevancy, freshness, number of citations, and downloads. In addition, it provides advanced rankings based on collaborative filtering techniques. The faceted filtering interface allows users to narrow search results based on a particular property or set of properties ("facets"), allowing users to manage large lists and explore the relationship between them. For any set or sub-set of records, the co-authorship network can be visualized in an interactive way, offering a view of the distribution of contributors and their inter-relationships. This provides an immediate way to detect groups and collaborations involved in a particular research field. For a majority of papers in Astronomy, our new interface will provide a list of related articles of potential interest. The recommendations are based on a number of factors, including text similarity, citations, and co-readership information. The new full-text search interface allows users to find all instances of particular words or phrases in the body of the articles in our full-text archive. This includes all of the scanned literature in ADS as well as a select portion of the current astronomical literature, including ApJ, ApJS, AJ, MNRAS, PASP, A&A, and soon additional content from Springer journals. Fulltext search results include a list of the matching papers as well as a list of "snippets" of text highlighting the context in which the search terms were found. ADS Labs is available at http://adslabs.org

Ensemble of random forests One vs. Rest classifiers for MCI and AD prediction using ANOVA cortical and subcortical feature selection and partial least squares.

PubMed

Ramírez, J; Górriz, J M; Ortiz, A; Martínez-Murcia, F J; Segovia, F; Salas-Gonzalez, D; Castillo-Barnes, D; Illán, I A; Puntonet, C G

2018-05-15

Alzheimer's disease (AD) is the most common cause of dementia in the elderly and affects approximately 30 million individuals worldwide. Mild cognitive impairment (MCI) is very frequently a prodromal phase of AD, and existing studies have suggested that people with MCI tend to progress to AD at a rate of about 10-15% per year. However, the ability of clinicians and machine learning systems to predict AD based on MRI biomarkers at an early stage is still a challenging problem that can have a great impact in improving treatments. The proposed system, developed by the SiPBA-UGR team for this challenge, is based on feature standardization, ANOVA feature selection, partial least squares feature dimension reduction and an ensemble of One vs. Rest random forest classifiers. With the aim of improving its performance when discriminating healthy controls (HC) from MCI, a second binary classification level was introduced that reconsiders the HC and MCI predictions of the first level. The system was trained and evaluated on an ADNI datasets that consist of T1-weighted MRI morphological measurements from HC, stable MCI, converter MCI and AD subjects. The proposed system yields a 56.25% classification score on the test subset which consists of 160 real subjects. The classifier yielded the best performance when compared to: (i) One vs. One (OvO), One vs. Rest (OvR) and error correcting output codes (ECOC) as strategies for reducing the multiclass classification task to multiple binary classification problems, (ii) support vector machines, gradient boosting classifier and random forest as base binary classifiers, and (iii) bagging ensemble learning. A robust method has been proposed for the international challenge on MCI prediction based on MRI data. The system yielded the second best performance during the competition with an accuracy rate of 56.25% when evaluated on the real subjects of the test set. Copyright © 2017 Elsevier B.V. All rights reserved.

Adélie Penguin Population Diet Monitoring by Analysis of Food DNA in Scats

PubMed Central

Jarman, Simon N.; McInnes, Julie C.; Faux, Cassandra; Polanowski, Andrea M.; Marthick, James; Deagle, Bruce E.; Southwell, Colin; Emmerson, Louise

2013-01-01

The Adélie penguin is the most important animal currently used for ecosystem monitoring in the Southern Ocean. The diet of this species is generally studied by visual analysis of stomach contents; or ratios of isotopes of carbon and nitrogen incorporated into the penguin from its food. There are significant limitations to the information that can be gained from these methods. We evaluated population diet assessment by analysis of food DNA in scats as an alternative method for ecosystem monitoring with Adélie penguins as an indicator species. Scats were collected at four locations, three phases of the breeding cycle, and in four different years. A novel molecular diet assay and bioinformatics pipeline based on nuclear small subunit ribosomal RNA gene (SSU rDNA) sequencing was used to identify prey DNA in 389 scats. Analysis of the twelve population sample sets identified spatial and temporal dietary change in Adélie penguin population diet. Prey diversity was found to be greater than previously thought. Krill, fish, copepods and amphipods were the most important food groups, in general agreement with other Adélie penguin dietary studies based on hard part or stable isotope analysis. However, our DNA analysis estimated that a substantial portion of the diet was gelatinous groups such as jellyfish and comb jellies. A range of other prey not previously identified in the diet of this species were also discovered. The diverse prey identified by this DNA-based scat analysis confirms that the generalist feeding of Adélie penguins makes them a useful indicator species for prey community composition in the coastal zone of the Southern Ocean. Scat collection is a simple and non-invasive field sampling method that allows DNA-based estimation of prey community differences at many temporal and spatial scales and provides significant advantages over alternative diet analysis approaches. PMID:24358158

Poly β-cyclodextrin/TPdye nanomicelle-based two-photon nanoprobe for caspase-3 activation imaging in live cells and tissues.

PubMed

Yan, Huijuan; He, Leiliang; Zhao, Wenjie; Li, Jishan; Xiao, Yue; Yang, Ronghua; Tan, Weihong

2014-11-18

Two-photon excitation (TPE) with near-infrared (NIR) photons as the excitation source has important advantages over conventional one-photon excitation (OPE) in the field of biomedical imaging. β-cyclodextrin polymer (βCDP)-based two-photon absorption (TPA) fluorescent nanomicelle exhibits desirable two-photon-sensitized fluorescence properties, high photostability, high cell-permeability and excellent biocompatibility. By combination of the nanostructured two-photon dye (TPdye)/βCDP nanomicelle with the TPE technique, herein we have designed a TPdye/βCDP nanomicelle-based TPA fluorescent nanoconjugate for enzymatic activity assay in biological fluids, live cells and tissues. This sensing system is composed of a trans-4-[p-(N,N-diethylamino)styryl]-N-methylpyridinium iodide (DEASPI)/βCDP nanomicelle as TPA fluorophore and carrier vehicle for delivery of a specific peptide sequence to live cell through fast endocytosis, and an adamantine (Ad)-GRRRDEVDK-BHQ2 (black hole quencher 2) peptide (denoted as Ad-DEVD-BHQ2) anchored on the DEASPI/βCDP nanomicelle's surface to form TPA DEASPI/βCDP@Ad-DEVD-BHQ2 nanoconjugate by the βCD/Ad host-guest inclusion strategy. Successful in vitro and in vivo enzymatic activities assay of caspase-3 was demonstrated with this sensing strategy. Our results reveal that this DEASPI/βCDP@Ad-DEVD-BHQ2 nanoconjugate not only is a robust, sensitive and selective sensor for quantitative assay of caspase-3 in the complex biological environment but also can be efficiently delivered into live cells as well as tissues and act as a "signal-on" fluorescent biosensor for specific, high-contrast imaging of enzymatic activities. This DEASPI/βCDP@Ad-DEVD-BHQ2 nanoconjugate provides a new opportunity to screen enzyme inhibitors and evaluate the apoptosis-associated disease progression. Moreover, our design also provides a methodology model scheme for development of future TPdye/βCDP nanomicelle-based two-photon fluorescent probes for in vitro or in vivo determination of biological or biologically relevant species.

Adélie penguin population diet monitoring by analysis of food DNA in scats.

PubMed

Jarman, Simon N; McInnes, Julie C; Faux, Cassandra; Polanowski, Andrea M; Marthick, James; Deagle, Bruce E; Southwell, Colin; Emmerson, Louise

2013-01-01

The Adélie penguin is the most important animal currently used for ecosystem monitoring in the Southern Ocean. The diet of this species is generally studied by visual analysis of stomach contents; or ratios of isotopes of carbon and nitrogen incorporated into the penguin from its food. There are significant limitations to the information that can be gained from these methods. We evaluated population diet assessment by analysis of food DNA in scats as an alternative method for ecosystem monitoring with Adélie penguins as an indicator species. Scats were collected at four locations, three phases of the breeding cycle, and in four different years. A novel molecular diet assay and bioinformatics pipeline based on nuclear small subunit ribosomal RNA gene (SSU rDNA) sequencing was used to identify prey DNA in 389 scats. Analysis of the twelve population sample sets identified spatial and temporal dietary change in Adélie penguin population diet. Prey diversity was found to be greater than previously thought. Krill, fish, copepods and amphipods were the most important food groups, in general agreement with other Adélie penguin dietary studies based on hard part or stable isotope analysis. However, our DNA analysis estimated that a substantial portion of the diet was gelatinous groups such as jellyfish and comb jellies. A range of other prey not previously identified in the diet of this species were also discovered. The diverse prey identified by this DNA-based scat analysis confirms that the generalist feeding of Adélie penguins makes them a useful indicator species for prey community composition in the coastal zone of the Southern Ocean. Scat collection is a simple and non-invasive field sampling method that allows DNA-based estimation of prey community differences at many temporal and spatial scales and provides significant advantages over alternative diet analysis approaches.

Factors associated with added sugars intake among adolescents living in São Paulo, Brazil.

PubMed

Colucci, Ana Carolina A; Cesar, Chester L G; Marchioni, Dirce M L; Fisberg, Regina M

2012-08-01

To measure added sugars intake among adolescents and describe its demographic, socioeconomic, and nutritional status determinants. The study was conducted based on a household survey carried out between March and December 2003. Food intake was assessed through 24-hour food recalls, and an adjustment approach was applied using external variance estimates derived from 195 adolescents of the same age in 2007. Population-based cross-sectional study, city of São Paulo, Brazil. Seven hundred and ninety-three male (n = 410) and female (n = 383) adolescents aged 10-19 years. MEASURE OF OUTCOME: Foods with greater contributions toward the added sugars intake were identified. Multiple linear regression analysis was performed, with calories from added sugars as the dependent continuous variable and the remaining factors (socioeconomic, demographic, lifestyle, household condition, and food intake) as independent variables. The average contribution of added sugars to total energy value was 12.28% (95% confidence interval [CI]: 11.87-12.70) with no statistically significant sex difference (p > 0.05). Soft drinks were a major source of added sugars among the adolescents (34.2% among males and 32.0% among females), followed by sugars (sucrose and honey) and chocolate powder (around 11%). In the multiple linear regression analysis, the head of household's education level and calories from protein, fats, and carbohydrates other than sugars had an independent effect on added sugars intake. This study showed that the percentage contribution of added sugars to energy intake among adolescents in the city of São Paulo, Brazil, was above the current recommended levels. Socioeconomic condition (represented by the head of the household's education level) and macronutrient intake were shown to be determinants of sugars intake.

Use of Speech Analyses within a Mobile Application for the Assessment of Cognitive Impairment in Elderly People.

PubMed

Konig, Alexandra; Satt, Aharon; Sorin, Alex; Hoory, Ran; Derreumaux, Alexandre; David, Renaud; Robert, Phillippe H

2018-01-01

Various types of dementia and Mild Cognitive Impairment (MCI) are manifested as irregularities in human speech and language, which have proven to be strong predictors for the disease presence and progress ion. Therefore, automatic speech analytics provided by a mobile application may be a useful tool in providing additional indicators for assessment and detection of early stage dementia and MCI. 165 participants (subjects with subjective cognitive impairment (SCI), MCI patients, Alzheimer's disease (AD) and mixed dementia (MD) patients) were recorded with a mobile application while performing several short vocal cognitive tasks during a regular consultation. These tasks included verbal fluency, picture description, counting down and a free speech task. The voice recordings were processed in two steps: in the first step, vocal markers were extracted using speech signal processing techniques; in the second, the vocal markers were tested to assess their 'power' to distinguish between SCI, MCI, AD and MD. The second step included training automatic classifiers for detecting MCI and AD, based on machine learning methods, and testing the detection accuracy. The fluency and free speech tasks obtain the highest accuracy rates of classifying AD vs. MD vs. MCI vs. SCI. Using the data, we demonstrated classification accuracy as follows: SCI vs. AD = 92% accuracy; SCI vs. MD = 92% accuracy; SCI vs. MCI = 86% accuracy and MCI vs. AD = 86%. Our results indicate the potential value of vocal analytics and the use of a mobile application for accurate automatic differentiation between SCI, MCI and AD. This tool can provide the clinician with meaningful information for assessment and monitoring of people with MCI and AD based on a non-invasive, simple and low-cost method. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data

PubMed Central

Gibson, J; Russ, T C; Adams, M J; Clarke, T-K; Howard, D M; Hall, L S; Fernandez-Pujals, A M; Wigmore, E M; Hayward, C; Davies, G; Murray, A D; Smith, B H; Porteous, D J; Deary, I J; McIntosh, A M

2017-01-01

Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in older age and frequently co-occur. Numerous phenotypic studies based on clinical diagnoses suggest that a history of depression increases risk of subsequent AD, although the basis of this relationship is uncertain. Both illnesses are polygenic, and shared genetic risk factors could explain some of the observed association. We used genotype data to test whether MDD and AD have an overlapping polygenic architecture in two large population-based cohorts, Generation Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25 118), and whether age of depression onset influences any relationship. Using two complementary techniques, we found no evidence that the disorders are influenced by common genetic variants. Using linkage disequilibrium score regression with genome-wide association study (GWAS) summary statistics from the International Genomics of Alzheimer's Project, we report no significant genetic correlation between AD and MDD (rG=−0.103, P=0.59). Polygenic risk scores (PRS) generated using summary data from International Genomics of Alzheimer's Project (IGAP) and the Psychiatric Genomics Consortium were used to assess potential pleiotropy between the disorders. PRS for MDD were nominally associated with participant-recalled AD family history in GS:SFHS, although this association did not survive multiple comparison testing. AD PRS were not associated with depression status or late-onset depression, and a survival analysis showed no association between age of depression onset and genetic risk for AD. This study found no evidence to support a common polygenic structure for AD and MDD, suggesting that the comorbidity of these disorders is not explained by common genetic variants. PMID:28418403

Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia

PubMed Central

Wilson, Robert S.; Weuve, Jennifer; Barnes, Lisa L.; Evans, Denis A.

2015-01-01

Objective: To examine the relation of performance on brief cognitive tests to development of clinically diagnosed Alzheimer disease (AD) dementia over the following 18 years in a sample of African Americans and European Americans. Methods: A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants (55% African American and 61% female) aged 65 years and older residing in 4 Chicago neighborhoods. Time before AD dementia diagnosis was categorized into 6 groups corresponding to data collection periods: 0.1–0.9, 1.0–3.9, 4.0–6.9, 7.0–9.9, 10.0–12.9, and 13.0–17.9 years. Results: Of 2,125 participants without clinical AD dementia, 442 (21%) developed clinical AD dementia over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of AD dementia over the duration of the study. The magnitude of association between composite cognitive test score and development of AD dementia increased from an odds ratio of 3.39 (95% confidence interval 1.72, 6.67; p < 0.001) at 13.0–17.9 years to 9.84 (95% confidence interval 7.41, 13.06; p < 0.001) at 0.1–0.9 years, per SD increment. These associations were consistently larger among European Americans than among African Americans. Performance on individual cognitive tests of episodic memory, executive function, and global cognition also significantly predicted the development of AD dementia, with associations exhibiting a similar trend over 18 years. Conclusions: Our findings suggest that cognitive impairment may manifest in the preclinical phase of AD dementia substantially earlier than previously established. PMID:26109713

New Features in ADS Labs

NASA Astrophysics Data System (ADS)

Accomazzi, Alberto; Kurtz, M. J.; Henneken, E. A.; Grant, C. S.; Thompson, D.; Di Milia, G.; Luker, J.; Murray, S. S.

2013-01-01

The NASA Astrophysics Data System (ADS) has been working hard on updating its services and interfaces to better support our community's research needs. ADS Labs is a new interface built on the old tried-and-true ADS Abstract Databases, so all of ADS's content is available through it. In this presentation we highlight the new features that have been developed in ADS Labs over the last year: new recommendations, metrics, a citation tool and enhanced fulltext search. ADS Labs has long been providing article-level recommendations based on keyword similarity, co-readership and co-citation analysis of its corpus. We have now introduced personal recommendations, which provide a list of articles to be considered based on a individual user's readership history. A new metrics interface provides a summary of the basic impact indicators for a list of records. These include the total and normalized number of papers, citations, reads, and downloads. Also included are some of the popular indices such as the h, g and i10 index. The citation helper tool allows one to submit a set of records and obtain a list of top 10 papers which cite and/or are cited by papers in the original list (but which are not in it). The process closely resembles the network approach of establishing "friends of friends" via an analysis of the citation network. The full-text search service now covers more than 2.5 million documents, including all the major astronomy journals, as well as physics journals published by Springer, Elsevier, the American Physical Society, the American Geophysical Union, and all of the arXiv eprints. The full-text search interface interface allows users and librarians to dig deep and find words or phrases in the body of the indexed articles. ADS Labs is available at http://adslabs.org

Chronic Depressive Symptomatology in Mild Cognitive Impairment Is Associated with Frontal Atrophy Rate which Hastens Conversion to Alzheimer Dementia.

PubMed

Sacuiu, Simona; Insel, Philip S; Mueller, Susanne; Tosun, Duygu; Mattsson, Niklas; Jack, Clifford R; DeCarli, Charles; Petersen, Ronald; Aisen, Paul S; Weiner, Michael W; Mackin, R Scott

2016-02-01

Investigate the association of chronic depressive symptomatology (chrDS) with cortical atrophy rates and conversion to Alzheimer dementia (AD) over 3 years in mild cognitive impairment (MCI). In a multicenter, clinic-based study, MCI elderly participants were selected from the Alzheimer's Disease Neuroimaging Initiative repository, based on availability of both serial structural magnetic resonance imaging and chrDS endorsed on three depression-related items from the Neuropsychiatric Inventory Questionnaire (chrDS N = 32 or no depressive symptoms N = 62) throughout follow-up. Clinical and laboratory investigations were performed every 6 months during the first 2 years and yearly thereafter (median follow-up: 3 years; interquartile range: 1.5-4.0 years). Cortical atrophy rates in 16 predefined frontotemporoparietal regions affected in major depression and AD and the rate of incident AD at follow-up. ChrDS in a single domain amnestic MCI sample were associated with accelerated cortical atrophy in the frontal lobe and anterior cingulate but not with atrophy rates in temporomedial or other AD-affected regions. During follow-up, 38 participants (42.7%) developed AD. Participants with chrDS had 60% shorter conversion time to AD than those without depressive symptoms. This association remained significant in survival models adjusted for temporomedial atrophy rates and showed the same trend in models adjusted for frontal cortical atrophy rate, which all increased the risk of AD. Our results suggest that chrDS associated with progressive atrophy of frontal regions may represent an additional risk factor for conversion to dementia in MCI as opposite to representing typical prodromal AD symptomatology. Published by Elsevier Inc.

Design, synthesis and anticonvulsant properties of new N-Mannich bases derived from 3-phenylpyrrolidine-2,5-diones.

PubMed

Kamiński, Krzysztof; Obniska, Jolanta; Chlebek, Iwona; Wiklik, Beata; Rzepka, Sabina

2013-11-01

The synthesis and anticonvulsant properties of new N-Mannich bases of 3-phenyl- (9a-d), 3-(2-chlorophenyl)- (10a-d), 3-(3-chlorophenyl)- (11a-d) and 3-(4-chlorophenyl)-pyrrolidine-2,5-diones (12a-d) were described. The key synthetic strategies involve the formation of 3-substituted pyrrolidine-2,5-diones (5-8), and then aminoalkylation reaction (Mannich-type) with formaldehyde and corresponding secondary amines, which let to obtain the final compounds 9a-d, 10a-d, 11a-d and 12a-d in good yields. Initial anticonvulsant screening was performed in mice (ip) using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizures tests. The most effective compounds in mice were tested after oral administration in rats. The acute neurological toxicity was determined applying the minimal motor impairment rotarod test. The in vivo results revealed that numerous compounds were effective especially in the MES test (model of human tonic-clonic seizures). The most active in the MES seizures in rats was 1-[(4-benzyl-1-piperidyl)methyl]-3-(2-chlorophenyl)pyrrolidine-2,5-dione (10c) which showed ED50 value of 37.64mg/kg. It should be stressed that this molecule along with 9a, 9d and 10d showed protection in the psychomotor seizure test (6-Hz), which is known as an animal model of therapy-resistant epilepsy. Furthermore compounds 9a, 9d and 10d were also tested in the pilocarpine-induced status prevention (PISP) test to assess their potential effectiveness in status epilepticus. For the most promising molecule 9d an influence on human CYP3A4 isoform of P-450 cytochrome was studied in vitro. Copyright © 2013 Elsevier Ltd. All rights reserved.

Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease.

PubMed

Goozee, K G; Shah, T M; Sohrabi, H R; Rainey-Smith, S R; Brown, B; Verdile, G; Martins, R N

2016-02-14

Curcumin derived from turmeric is well documented for its anti-carcinogenic, antioxidant and anti-inflammatory properties. Recent studies show that curcumin also possesses neuroprotective and cognitive-enhancing properties that may help delay or prevent neurodegenerative diseases, including Alzheimer's disease (AD). Currently, clinical diagnosis of AD is onerous, and it is primarily based on the exclusion of other causes of dementia. In addition, phase III clinical trials of potential treatments have mostly failed, leaving disease-modifying interventions elusive. AD can be characterised neuropathologically by the deposition of extracellular β amyloid (Aβ) plaques and intracellular accumulation of tau-containing neurofibrillary tangles. Disruptions in Aβ metabolism/clearance contribute to AD pathogenesis. In vitro studies have shown that Aβ metabolism is altered by curcumin, and animal studies report that curcumin may influence brain function and the development of dementia, because of its antioxidant and anti-inflammatory properties, as well as its ability to influence Aβ metabolism. However, clinical studies of curcumin have revealed limited effects to date, most likely because of curcumin's relatively low solubility and bioavailability, and because of selection of cohorts with diagnosed AD, in whom there is already major neuropathology. However, the fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy. The aim of this paper is to review the current evidence supporting an association between curcumin and modulation of AD pathology, including in vitro and in vivo studies. We also review the use of curcumin in emerging retinal imaging technology, as a fluorochrome for AD diagnostics.

Comparison of the immunogenicity and protection against bovine tuberculosis following immunization by BCG-priming and boosting with adenovirus or protein based vaccines.

PubMed

Dean, G; Whelan, A; Clifford, D; Salguero, F J; Xing, Z; Gilbert, S; McShane, H; Hewinson, R G; Vordermeier, M; Villarreal-Ramos, B

2014-03-05

There is a requirement for vaccines or vaccination strategies that confer better protection against TB than the current live attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine for use in cattle. Boosting with recombinant viral vectors expressing mycobacterial proteins, such as Ag85A, has shown a degree of promise as a strategy for improving on the protection afforded by BCG. Experiments in small animal models have indicated that broadening the immune response to include mycobacterial antigens other than Ag85A, such as Rv0288, induced by boosting with Ad5 constructs has a direct effect on the protection afforded against TB. Here, we compared the immunogenicity and protection against challenge with M. bovis afforded by boosting BCG-vaccinated cattle with a human type 5 (Ad5)-based vaccine expressing the mycobacterial antigens Ag85A (Ad5-85A); or Ag85A, Rv0251, Rv0287 and Rv0288 (Ad5-TBF); or with protein TBF emulsified in adjuvant (Adj-TBF). Boosting with TBF broaden the immune response. The kinetics of Ad5-TBF and Adj-TBF were shown to be different, with effector T cell responses from the latter developing more slowly but being more durable than those induced by Ad5-TBF. No increase in protection compared to BCG alone was afforded by Ad5-TBF or Adj-TBF by gross pathology or bacteriology. Using histopathology, as a novel parameter of protection, we show that boosting BCG vaccinated cattle with Ad5-85A induced significantly better protection than BCG alone. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Predictors of driving safety in early Alzheimer disease.

PubMed

Dawson, J D; Anderson, S W; Uc, E Y; Dastrup, E; Rizzo, M

2009-02-10

To measure the association of cognition, visual perception, and motor function with driving safety in Alzheimer disease (AD). Forty drivers with probable early AD (mean Mini-Mental State Examination score 26.5) and 115 elderly drivers without neurologic disease underwent a battery of cognitive, visual, and motor tests, and drove a standardized 35-mile route in urban and rural settings in an instrumented vehicle. A composite cognitive score (COGSTAT) was calculated for each subject based on eight neuropsychological tests. Driving safety errors were noted and classified by a driving expert based on video review. Drivers with AD committed an average of 42.0 safety errors/drive (SD = 12.8), compared to an average of 33.2 (SD = 12.2) for drivers without AD (p < 0.0001); the most common errors were lane violations. Increased age was predictive of errors, with a mean of 2.3 more errors per drive observed for each 5-year age increment. After adjustment for age and gender, COGSTAT was a significant predictor of safety errors in subjects with AD, with a 4.1 increase in safety errors observed for a 1 SD decrease in cognitive function. Significant increases in safety errors were also found in subjects with AD with poorer scores on Benton Visual Retention Test, Complex Figure Test-Copy, Trail Making Subtest-A, and the Functional Reach Test. Drivers with Alzheimer disease (AD) exhibit a range of performance on tests of cognition, vision, and motor skills. Since these tests provide additional predictive value of driving performance beyond diagnosis alone, clinicians may use these tests to help predict whether a patient with AD can safely operate a motor vehicle.

Genome-Wide Significant Association between Alcohol Dependence and a Variant in the ADH Gene Cluster

PubMed Central

Frank, Josef; Cichon, Sven; Treutlein, Jens; Ridinger, Monika; Mattheisen, Manuel; Hoffmann, Per; Herms, Stefan; Wodarz, Norbert; Soyka, Michael; Zill, Peter; Maier, Wolfgang; Mössner, Rainald; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Schmäl, Christine; Steffens, Michael; Lucae, Susanne; Ising, Marcus; Müller-Myhsok, Bertram; Nöthen, Markus M; Mann, Karl; Kiefer, Falk; Rietschel, Marcella

2011-01-01

Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome-wide association study (GWAS). The sample comprised 1,333 male in-patients with severe DSM-IV AD and 2,168 controls. These included 487 patients and 1,358 controls from a previous GWAS study by our group. All individuals were of German descent. Single marker tests and a polygenic score based analysis to assess the combined contribution of multiple markers with small effects were performed. The SNP rs1789891, which is located between the ADH1B and ADH1C genes, achieved genome-wide significance (p=1.27E–8; OR=1.46). Other markers from this region were also associated with AD, and conditional analyses indicated that these made a partially independent contribution. The SNP rs1789891 is in complete linkage disequilibrium with the functional Arg272Gln variant (p=1.24E–7, OR=1.31) of the ADH1C gene, which has been reported to modify the rate of ethanol oxidation to acetaldehyde in vitro. A polygenic score based approach produced a significant result (p=9.66E–9). This is the first GWAS of AD to provide genome-wide significant support for the role of the ADH gene cluster and to suggest a polygenic component to the etiology of AD. The latter result suggests that many more AD susceptibility genes still await identification. PMID:22004471

Rationale and clinical data supporting nutritional intervention in Alzheimer's disease.

PubMed

Engelborghs, S; Gilles, C; Ivanoiu, A; Vandewoude, M

2014-01-01

Adequate nutrition plays an important role in the maintenance of cognitive function, particularly during aging. Malnutrition is amongst the risk factors for developing mild cognitive impairment (MCI) and Alzheimer's disease (AD). Epidemiological studies have associated deficiencies in some nutrients with a higher risk of cognitive dysfunction and/or AD. Cognitive decline in AD is correlated with synaptic loss and many of the components required to maintain optimal synaptic function are derived from dietary sources. As synapses are part of the neuronal membrane and are continuously being remodelled, the availability of sufficient levels of nutritional precursors (mainly uridine monophosphate, choline and omega-3 fatty acids) to make the phospholipids required to build neuronal membranes may have beneficial effects on synaptic degeneration in AD. In addition, B-vitamins, phospholipids and other micronutrients act as cofactors to enhance the supply of precursors required to make neuronal membranes and synapses. Despite this, no randomized controlled trial has hitherto provided evidence that any single nutrient has a beneficial effect on cognition or lowers the risk for AD. However, a multi-target approach using combinations of (micro)nutrients might have beneficial effects on cognitive function in neurodegenerative brain disorders like AD leading to synaptic degeneration. Here we review the clinical evidence for supplementation, based on a multi-target approach with a focus on key nutrients with a proposed role in synaptic dysfunction. Based on preclinical evidence, a nutrient mixture, Souvenaid(®) (Nutricia N.V., Zoetermeer, The Netherlands) was developed. Clinical trials with Souvenaid(®) have shown improved memory performance in patients with mild AD. Further clinical trials to evaluate the effects of nutritional intervention in MCI and early dementia due to AD are on-going.

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data.

PubMed

Gibson, J; Russ, T C; Adams, M J; Clarke, T-K; Howard, D M; Hall, L S; Fernandez-Pujals, A M; Wigmore, E M; Hayward, C; Davies, G; Murray, A D; Smith, B H; Porteous, D J; Deary, I J; McIntosh, A M

2017-04-18

Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in older age and frequently co-occur. Numerous phenotypic studies based on clinical diagnoses suggest that a history of depression increases risk of subsequent AD, although the basis of this relationship is uncertain. Both illnesses are polygenic, and shared genetic risk factors could explain some of the observed association. We used genotype data to test whether MDD and AD have an overlapping polygenic architecture in two large population-based cohorts, Generation Scotland's Scottish Family Health Study (GS:SFHS; N=19 889) and UK Biobank (N=25 118), and whether age of depression onset influences any relationship. Using two complementary techniques, we found no evidence that the disorders are influenced by common genetic variants. Using linkage disequilibrium score regression with genome-wide association study (GWAS) summary statistics from the International Genomics of Alzheimer's Project, we report no significant genetic correlation between AD and MDD (r G =-0.103, P=0.59). Polygenic risk scores (PRS) generated using summary data from International Genomics of Alzheimer's Project (IGAP) and the Psychiatric Genomics Consortium were used to assess potential pleiotropy between the disorders. PRS for MDD were nominally associated with participant-recalled AD family history in GS:SFHS, although this association did not survive multiple comparison testing. AD PRS were not associated with depression status or late-onset depression, and a survival analysis showed no association between age of depression onset and genetic risk for AD. This study found no evidence to support a common polygenic structure for AD and MDD, suggesting that the comorbidity of these disorders is not explained by common genetic variants.

Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia.

PubMed

Rajan, Kumar B; Wilson, Robert S; Weuve, Jennifer; Barnes, Lisa L; Evans, Denis A

2015-09-08

To examine the relation of performance on brief cognitive tests to development of clinically diagnosed Alzheimer disease (AD) dementia over the following 18 years in a sample of African Americans and European Americans. A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants (55% African American and 61% female) aged 65 years and older residing in 4 Chicago neighborhoods. Time before AD dementia diagnosis was categorized into 6 groups corresponding to data collection periods: 0.1-0.9, 1.0-3.9, 4.0-6.9, 7.0-9.9, 10.0-12.9, and 13.0-17.9 years. Of 2,125 participants without clinical AD dementia, 442 (21%) developed clinical AD dementia over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of AD dementia over the duration of the study. The magnitude of association between composite cognitive test score and development of AD dementia increased from an odds ratio of 3.39 (95% confidence interval 1.72, 6.67; p < 0.001) at 13.0-17.9 years to 9.84 (95% confidence interval 7.41, 13.06; p < 0.001) at 0.1-0.9 years, per SD increment. These associations were consistently larger among European Americans than among African Americans. Performance on individual cognitive tests of episodic memory, executive function, and global cognition also significantly predicted the development of AD dementia, with associations exhibiting a similar trend over 18 years. Our findings suggest that cognitive impairment may manifest in the preclinical phase of AD dementia substantially earlier than previously established. © 2015 American Academy of Neurology.

Neuroprotective Effect of SLM, a Novel Carbazole-Based Fluorophore, on SH-SY5Y Cell Model and 3xTg-AD Mouse Model of Alzheimer's Disease.

PubMed

Wu, Xiaoli; Kosaraju, Jayasankar; Zhou, Wei; Tam, Kin Yip

2017-03-15

Amyloid β (Aβ) peptide aggregating to form a neurotoxic plaque, leading to cognitive deficits, is believed to be one of the plausible mechanisms for Alzheimer's disease (AD). Inhibiting Aβ aggregation is supposed to offer a neuroprotective effect to ameliorate AD. A previous report has shown that SLM, a carbazole-based fluorophore, binds to Aβ to inhibit the aggregation. However, it is not entirely clear whether the inhibition of Aβ aggregation alone would lead to the anticipated neuroprotective effects. In the current study, we intended to examine the protective action of SLM against Aβ-induced neurotoxicity in vitro and to evaluate if SLM can decrease the cognitive and behavioral deficits observed in triple transgenic AD mouse model (3xTg-AD). In the in vitro study, neurotoxicity induced by Aβ42 in human neuroblastoma (SH-SY5Y) cells was found to be reduced through the treatment with SLM. In the in vivo study, following one month SLM intraperitoneal injection (1, 2, and 4 mg/kg), 3xTg-AD mice were tested on Morris water maze (MWM) and Y-maze for their cognitive ability and sacrificed for biochemical estimations. Results show that SLM treatment improved the learning and memory ability in 3xTg-AD mice in MWM and Y-maze tasks. SLM also mitigated the amyloid burden by decreasing brain Aβ40 and Aβ42 levels and reduced tau phosphorylation, glycogen synthase kinase-3β activity, and neuro-inflammation. From our observations, SLM shows neuroprotection in SH-SY5Y cells against Aβ42 and also in 3xTg-AD mouse model by mitigating the pathological features and behavioral impairments.

Exploration on Wire Discharge Machining Added Powder for Metal-Based Diamond Grinding Wheel on Wire EDM Dressing and Truing of Grinding Tungsten Carbide Material

NASA Astrophysics Data System (ADS)

Chow, H. M.; Yang, L. D.; Lin, Y. C.; Lin, C. L.

2017-12-01

In this paper, the effects of material removal rate and abrasive grain protrusion on the metal-based diamond grinding wheel were studied to find the optimal parameters for adding powder and wire discharge. In addition, this kind of electric discharge method to add powder on the metal-based diamond grinding wheel on line after dressing and truing will be applied on tungsten carbide to study the grinding material removal rate, grinding wheel wear, surface roughness, and surface micro-hardness.

Recognition and treatment of Alzheimer's disease: a case-based review.

PubMed

Marseille, Dana M; Silverman, Daniel H S

2006-01-01

Early recognition and treatment initiation are pivotal in managing Alzheimer's disease (AD). Once a diagnosis of AD is made, a treatment plan is developed and should include treatment initiation with cholinesterase inhibitors (ChEIs) to improve cognition, management of comorbid conditions, and treat behavioral symptoms. Caregiver compliance is integral to AD treatment success. The purpose of this report is to present two real case studies of "suspected" AD or related dementia and stress the significance of early and accurate diagnosis in disease management. In case 1, a caregiver reports gradual but progressive loss of memory, and the patient himself complains of memory impairment. Neuroimaging analysis confirms "typical " AD. In case 2, initiation of ChEI therapy is followed by substantial clinical improvement in the face of a complex medical picture, and neuroimaging revealing more neurodegenerative changes than could be accounted for by "pure" AD.

Cost-effective advertising through TV and newspaper "banner" ads.

PubMed

Gombeski, William R; Taylor, Jan; Krauss, Katie; Medeiros, Clayton

2003-01-01

Banner ads, small strip ads in newspapers used to specifically promote an information piece, were introduced into one newspaper in the Connecticut market in 1999 by Yale-New Haven Hospital (YNHH). Based on their success, the concept was expanded to six additional newspapers in late 2000 and to TV in the summer of 2001. Between 2000-2002, even as the overall marketing/advertising budget declined 30%, switching advertising dollars from image/display ads to banner ads resulted in consumer awareness of YNHH increasing from 29% to 42%. Perception of YNHH as "the advanced medicine" hospital grew from 22% to 40% during the same period. The specific strategic and operational actions generated since the implementation of the program are detailed and the advantages and disadvantages of this banner advertising approach are discussed. Banner ads may offer an alternative approach for organizations to advertise their products and programs.

Touching the base: heart-warming ads from the 2016 U.S. election moved viewers to partisan tears.

PubMed

Seibt, Beate; Schubert, Thomas W; Zickfeld, Janis H; Fiske, Alan P

2018-03-07

Some political ads used in the 2016 U.S. election evoked feelings colloquially known as being moved to tears. We conceptualise this phenomenon as a positive social emotion that appraises and motivates communal relations, is accompanied by physical sensations (including lachrymation, piloerection, chest warmth), and often labelled metaphorically. We surveyed U.S. voters in the fortnight before the 2016 U.S. election. Selected ads evoked the emotion completely and reliably, but in a partisan fashion: Clinton voters were moved to tears by three selected Clinton ads, and Trump voters were moved to tears by two Trump ads. Viewers were much less moved by ads of the candidate they did not support. Being moved to tears predicted intention to vote for the candidate depicted. We conclude that some contemporary political advertising is able to move its audience to tears, and thereby motivates support.

A Pragmatic Approach to Patch Testing Atopic Dermatitis Patients: Clinical Recommendations Based on Expert Consensus Opinion.

PubMed

Chen, Jennifer K; Jacob, Sharon E; Nedorost, Susan T; Hanifin, Jon M; Simpson, Eric L; Boguniewicz, Mark; Watsky, Kalman L; Lugo-Somolinos, Aida; Hamann, Carsten R; Eberting, Cheryl Lee; Silverberg, Jonathan I; Thyssen, Jacob P

2016-01-01

Allergic contact dermatitis (ACD) may complicate the clinical course of atopic dermatitis (AD), and patch testing remains the criterion standard for diagnosing ACD. To date, there have been no guidelines or consensus recommendations on when and how to patch test individuals with AD. Failure to patch test when appropriate may result in overlooking an important and potentially curable complicating comorbidity. In this article, we present consensus recommendations regarding when to perform patch testing in the AD patient, best practices, and common pitfalls. Patch testing should be considered in AD patients with dermatitis that fails to improve with topical therapy; with atypical/changing distribution of dermatitis, or pattern suggestive of ACD; with therapy-resistant hand eczema in the working population; with adult- or adolescent-onset AD; and/or before initiating systemic immunosuppressants for the treatment of dermatitis. A suggested patch testing algorithm for AD patients is provided.

Raman spectroscopy of blood serum for Alzheimer's disease diagnostics: specificity relative to other types of dementia

PubMed Central

Ryzhikova, Elena; Kazakov, Oleksandr; Halamkova, Lenka; Celmins, Dzintra; Malone, Paula; Molho, Eric; Zimmerman, Earl A.; Lednev, Igor K.

2015-01-01

The key moment for efficiently and accurately diagnosing dementia occurs during the early stages. This is particularly true for Alzheimer's disease (AD). In this proof-of-concept study, we applied near infrared (NIR) Raman microspectroscopy of blood serum together with advanced multivariate statistics for the selective identification of AD. We analyzed data from 20 AD patients, 18 patients with other neurodegenerative dementias (OD) and 10 healthy control (HC) subjects. NIR Raman microspectroscopy differentiated patients with more than 95% sensitivity and specificity. We demonstrated the high discriminative power of artificial neural network (ANN) classification models, thus revealing the high potential of this developed methodology for the differential diagnosis of AD. Raman spectroscopic, blood-based tests may aid clinical assessments for the effective and accurate differential diagnosis of AD, decrease the labor, time and cost of diagnosis, and be useful for screening patient populations for AD development and progression. PMID:25256347

Quantitation of heteroplasmy of mtDNA sequence variants identified in a population of AD patients and controls by array-based resequencing.

PubMed

Coon, Keith D; Valla, Jon; Szelinger, Szabolics; Schneider, Lonnie E; Niedzielko, Tracy L; Brown, Kevin M; Pearson, John V; Halperin, Rebecca; Dunckley, Travis; Papassotiropoulos, Andreas; Caselli, Richard J; Reiman, Eric M; Stephan, Dietrich A

2006-08-01

The role of mitochondrial dysfunction in the pathogenesis of Alzheimer's disease (AD) has been well documented. Though evidence for the role of mitochondria in AD seems incontrovertible, the impact of mitochondrial DNA (mtDNA) mutations in AD etiology remains controversial. Though mutations in mitochondrially encoded genes have repeatedly been implicated in the pathogenesis of AD, many of these studies have been plagued by lack of replication as well as potential contamination of nuclear-encoded mitochondrial pseudogenes. To assess the role of mtDNA mutations in the pathogenesis of AD, while avoiding the pitfalls of nuclear-encoded mitochondrial pseudogenes encountered in previous investigations and showcasing the benefits of a novel resequencing technology, we sequenced the entire coding region (15,452 bp) of mtDNA from 19 extremely well-characterized AD patients and 18 age-matched, unaffected controls utilizing a new, reliable, high-throughput array-based resequencing technique, the Human MitoChip. High-throughput, array-based DNA resequencing of the entire mtDNA coding region from platelets of 37 subjects revealed the presence of 208 loci displaying a total of 917 sequence variants. There were no statistically significant differences in overall mutational burden between cases and controls, however, 265 independent sites of statistically significant change between cases and controls were identified. Changed sites were found in genes associated with complexes I (30.2%), III (3.0%), IV (33.2%), and V (9.1%) as well as tRNA (10.6%) and rRNA (14.0%). Despite their statistical significance, the subtle nature of the observed changes makes it difficult to determine whether they represent true functional variants involved in AD etiology or merely naturally occurring dissimilarity. Regardless, this study demonstrates the tremendous value of this novel mtDNA resequencing platform, which avoids the pitfalls of erroneously amplifying nuclear-encoded mtDNA pseudogenes, and our proposed analysis paradigm, which utilizes the availability of raw signal intensity values for each of the four potential alleles to facilitate quantitative estimates of mtDNA heteroplasmy. This information provides a potential new target for burgeoning diagnostics and therapeutics that could truly assist those suffering from this devastating disorder.

Can Genetic Analysis of Putative Blood Alzheimer’s Disease Biomarkers Lead to Identification of Susceptibility Loci?

PubMed Central

Huebinger, Ryan M.; Shewale, Shantanu J.; Koenig, Jessica L.; Mitchel, Jeffrey S.; O’Bryant, Sid E.; Waring, Stephen C.; Diaz-Arrastia, Ramon; Chasse, Scott

2015-01-01

Although 24 Alzheimer’s disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10-7. Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel genetic interactions and should be further investigated. PMID:26625115

Developing a dementia-specific health state classification system for a new preference-based instrument AD-5D.

PubMed

Nguyen, Kim-Huong; Mulhern, Brendan; Kularatna, Sanjeewa; Byrnes, Joshua; Moyle, Wendy; Comans, Tracy

2017-01-25

With an ageing population, the number of people with dementia is rising. The economic impact on the health care system is considerable and new treatment methods and approaches to dementia care must be cost effective. Economic evaluation requires valid patient reported outcome measures, and this study aims to develop a dementia-specific health state classification system based on the Quality of Life for Alzheimer's disease (QOL-AD) instrument (nursing home version). This classification system will subsequently be valued to generate a preference-based measure for use in the economic evaluation of interventions for people with dementia. We assessed the dimensionality of the QOL-AD to develop a new classification system. This was done using exploratory and confirmatory factor analysis and further assessment of the structure of the measure to ensure coverage of the key areas of quality of life. Secondly, we used Rasch analysis to test the psychometric performance of the items, and select item(s) to describe each dimension. This was done on 13 items of the QOL-AD (excluding two general health items) using a sample of 284 residents living in long-term care facilities in Australia who had a diagnosis of dementia. A five dimension classification system is proposed resulting from the three factor structure (defined as 'interpersonal environment', 'physical health' and 'self-functioning') derived from the factor analysis and two factors ('memory' and 'mood') from the accompanying review. For the first three dimensions, Rasch analysis selected three questions of the QOL-AD ('living situation', 'physical health', and 'do fun things') with memory and mood questions representing their own dimensions. The resulting classification system (AD-5D) includes many of the health-related quality of life dimensions considered important to people with dementia, including mood, global function and skill in daily living. The development of the AD-5D classification system is an important step in the future application of the widely used QOL-AD in economic evaluations. Future valuation studies will enable this tool to be used to calculate quality adjusted life years to evaluate treatments and interventions for people diagnosed with mild to moderate dementia.

Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci?

PubMed

Barber, Robert C; Phillips, Nicole R; Tilson, Jeffrey L; Huebinger, Ryan M; Shewale, Shantanu J; Koenig, Jessica L; Mitchel, Jeffrey S; O'Bryant, Sid E; Waring, Stephen C; Diaz-Arrastia, Ramon; Chasse, Scott; Wilhelmsen, Kirk C

2015-01-01

Although 24 Alzheimer's disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10(-7). Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel genetic interactions and should be further investigated.

Coffee, tea, and caffeine consumption and prevention of late-life cognitive decline and dementia: a systematic review.

PubMed

Panza, F; Solfrizzi, V; Barulli, M R; Bonfiglio, C; Guerra, V; Osella, A; Seripa, D; Sabbà, C; Pilotto, A; Logroscino, G

2015-03-01

A prolonged preclinical phase of more than two decades before the onset of dementia suggested that initial brain changes of Alzheimer's disease (AD) and the symptoms of advanced AD may represent a unique continuum. Given the very limited therapeutic value of drugs currently used in the treatment of AD and dementia, preventing or postponing the onset of AD and delaying or slowing its progression are becoming mandatory. Among possible reversible risk factors of dementia and AD, vascular, metabolic, and lifestyle-related factors were associated with the development of dementia and late-life cognitive disorders, opening new avenues for the prevention of these diseases. Among diet-associated factors, coffee is regularly consumed by millions of people around the world and owing to its caffeine content, it is the best known psychoactive stimulant resulting in heightened alertness and arousal and improvement of cognitive performance. Besides its short-term effect, some case-control and cross-sectional and longitudinal population-based studies evaluated the long-term effects on brain function and provided some evidence that coffee, tea, and caffeine consumption or higher plasma caffeine levels may be protective against cognitive impairment/decline and dementia. In particular, several cross-sectional and longitudinal population-based studies suggested a protective effect of coffee, tea, and caffeine use against late-life cognitive impairment/decline, although the association was not found in all cognitive domains investigated and there was a lack of a distinct dose-response association, with a stronger effect among women than men. The findings on the association of coffee, tea, and caffeine consumption or plasma caffeine levels with incident mild cognitive impairment and its progression to dementia were too limited to draw any conclusion. Furthermore, for dementia and AD prevention, some studies with baseline examination in midlife pointed to a lack of association, although other case-control and longitudinal population-based studies with briefer follow-up periods supported favourable effects of coffee, tea, and caffeine consumption against AD. Larger studies with longer follow-up periods should be encouraged, addressing other potential bias and confounding sources, so hopefully opening new ways for diet-related prevention of dementia and AD.

Estimation of chromophoric dissolved organic matter in the Mississippi and Atchafalaya river plume regions using above-surface hyperspectral remote sensing

NASA Astrophysics Data System (ADS)

Zhu, Weining; Yu, Qian; Tian, Yong Q.; Chen, Robert F.; Gardner, G. Bernard

2011-02-01

A method for the inversion of hyperspectral remote sensing was developed to determine the absorption coefficient for chromophoric dissolved organic matter (CDOM) in the Mississippi and Atchafalaya river plume regions and the northern Gulf of Mexico, where water types vary from Case 1 to turbid Case 2. Above-surface hyperspectral remote sensing data were measured by a ship-mounted spectroradiometer and then used to estimate CDOM. Simultaneously, water absorption and attenuation coefficients, CDOM and chlorophyll fluorescence, turbidities, and other related water properties were also measured at very high resolution (0.5-2 m) using in situ, underwater, and flow-through (shipboard, pumped) optical sensors. We separate ag, the absorption coefficient a of CDOM, from adg (a of CDOM and nonalgal particles) based on two absorption-backscattering relationships. The first is between ad (a of nonalgal particles) and bbp (total particulate backscattering coefficient), and the second is between ap (a of total particles) and bbp. These two relationships are referred as ad-based and ap-based methods, respectively. Consequently, based on Lee's quasi-analytical algorithm (QAA), we developed the so-called Extended Quasi-Analytical Algorithm (QAA-E) to decompose adg, using both ad-based and ap-based methods. The absorption-backscattering relationships and the QAA-E were tested using synthetic and in situ data from the International Ocean-Colour Coordinating Group (IOCCG) as well as our own field data. The results indicate the ad-based method is relatively better than the ap-based method. The accuracy of CDOM estimation is significantly improved by separating ag from adg (R2 = 0.81 and 0.65 for synthetic and in situ data, respectively). The sensitivities of the newly introduced coefficients were also analyzed to ensure QAA-E is robust.

Fuel consumption of ADS-B and non-ADS-B helicopter operation in the Gulf of Mexico

DOT National Transportation Integrated Search

2013-07-01

Automatic Dependent Surveillance Broadcast (ADSB) is a key enabling technology for the Next Generation Air Transportation System (NextGen) in the United States. The NextGen system replaces the current ground based commandandcontrol syste...

Sweat glucose and GLUT2 expression in atopic dermatitis: Implication for clinical manifestation and treatment

PubMed Central

Ono, Emi; Mori, Yuki; Yoshioka, Yoshichika; Nomura, Yuko; Munetsugu, Takichi; Yokozeki, Hiroo; Katayama, Ichiro

2018-01-01

Sweat includes active components and metabolites, which are needed to maintain skin homeostasis. Component changes in sweat derived from atopic dermatitis (AD) have been reported. To investigate the influence of sweat components on the pathogenesis of AD, we performed a multifaceted assessment, including nuclear magnetic resonance spectroscopy-based metabolomic analysis, and linked these features to clinical features of AD. Distinctive properties of AD sweat are the quite-variation in protein, anti-microbial peptides and glucose concentrations. pH, sodium, and other salt levels in sweat of AD were comparable to that of healthy subjects. Sweat from AD patients with acute inflammation had a more prominent increase in glucose concentration than sweat from healthy individuals or those with AD with chronic inflammation. Topical glucose application delayed recovery of transepidermal water loss in barrier-disrupted mice. Furthermore, the glucose transporter GLUT2 was highly expressed in the lumen of sweat glands from AD patients. AD patients with chronic inflammation had significantly increased GLUT2 mRNA expression and near normal sweat glucose levels. Despite the small sample size in our study, we speculate that the increased glucose levels might be affected by AD severity and phenotype. We hope that this report will bring novel insight into the impact of sweat components on the clinical manifestation of AD. PMID:29677207

Evaluation of Oxidant-Antioxidant Balance in Children with Atopic Dermatitis: A Case-Control Study.

PubMed

Uysal, Pınar; Avcil, Sibelnur; Abas, Burçin İrem; Yenisey, Çiğdem

2016-10-01

Increased reactive oxygen species (ROS) and oxidative stress (OS) has been reported in many allergic and inflammatory skin diseases, including urticaria, psoriasis, and atopic dermatitis (AD). Melatonin is a hormone secreted from the pineal gland and is a potent antioxidant. The aim of the study was to measure serum antioxidant melatonin, oxidants of nitric oxide (NO), and malondialdehyde levels to calculate the serum oxidant-antioxidant balance based on the NO/melatonin and malondialdehyde/melatonin ratios and to determine the correlation with the disease severity in children with AD. Seventy-three children with AD and 67 healthy controls were included in the study. The clinical diagnosis of AD was based on the diagnostic criteria of Hanifin-Rajka. The severity of AD was evaluated by the scoring AD (SCORAD) index, and atopy was determined by skin prick tests (SPTs) with commercial extracts. The OS-related parameters of serum melatonin, NO, malondialdehyde, and the NO/melatonin and malondialdehyde/melatonin ratios were calculated and compared with the results of healthy controls. Serum melatonin levels were higher (p < 0.0001) and serum NO levels and the NO/melatonin and malondialdehyde/melatonin ratios were lower in children with AD than in healthy controls (p = 0.045, p < 0.0001, p < 0.0001, respectively). There was no difference between children with AD and healthy controls in terms of serum malondialdehyde levels (p = 0.119). Serum melatonin levels were significantly lower in severe AD than in mild AD (p = 0.012). However, in terms of serum melatonin levels, there was no difference between mild and moderate AD (p = 0.742) and moderate to severe AD (p = 0.301). There was no significant difference in serum NO and malondialdehyde levels and NO/melatonin and malondialdehyde/melatonin ratios among children with mild, moderate, and severe AD (p > 0.05). A negative correlation was found between serum melatonin levels and the SCORAD index (r = -0.252, p = 0.031), and a positive correlation was found between NO/melatonin and malondialdehyde/melatonin ratios (r = 0.511, p < 0.0001). There was no statistically significant relationship between age (≤24 or >24 months), disease duration (≤6 or >6 months), and sex for the OS-related parameters (p > 0.05). The serum oxidant-antioxidant balance was impaired in children with AD. Serum melatonin levels were higher in children with AD; however, this was negatively correlated with disease severity. Serum NO levels and NO/melatonin and malondialdehyde/melatonin ratios were lower in children with AD than in healthy controls. Melatonin might be used as a promising antioxidant to evaluate disease severity in children with AD. Thus, further studies are needed to clarify the role of melatonin in AD pathogenesis.

Structural MRI-based detection of Alzheimer's disease using feature ranking and classification error.

PubMed

Beheshti, Iman; Demirel, Hasan; Farokhian, Farnaz; Yang, Chunlan; Matsuda, Hiroshi

2016-12-01

This paper presents an automatic computer-aided diagnosis (CAD) system based on feature ranking for detection of Alzheimer's disease (AD) using structural magnetic resonance imaging (sMRI) data. The proposed CAD system is composed of four systematic stages. First, global and local differences in the gray matter (GM) of AD patients compared to the GM of healthy controls (HCs) are analyzed using a voxel-based morphometry technique. The aim is to identify significant local differences in the volume of GM as volumes of interests (VOIs). Second, the voxel intensity values of the VOIs are extracted as raw features. Third, the raw features are ranked using a seven-feature ranking method, namely, statistical dependency (SD), mutual information (MI), information gain (IG), Pearson's correlation coefficient (PCC), t-test score (TS), Fisher's criterion (FC), and the Gini index (GI). The features with higher scores are more discriminative. To determine the number of top features, the estimated classification error based on training set made up of the AD and HC groups is calculated, with the vector size that minimized this error selected as the top discriminative feature. Fourth, the classification is performed using a support vector machine (SVM). In addition, a data fusion approach among feature ranking methods is introduced to improve the classification performance. The proposed method is evaluated using a data-set from ADNI (130 AD and 130 HC) with 10-fold cross-validation. The classification accuracy of the proposed automatic system for the diagnosis of AD is up to 92.48% using the sMRI data. An automatic CAD system for the classification of AD based on feature-ranking method and classification errors is proposed. In this regard, seven-feature ranking methods (i.e., SD, MI, IG, PCC, TS, FC, and GI) are evaluated. The optimal size of top discriminative features is determined by the classification error estimation in the training phase. The experimental results indicate that the performance of the proposed system is comparative to that of state-of-the-art classification models. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hardware-Enabled Security Through On-Chip Reconfigurable Fabric

DTIC Science & Technology

2016-02-05

SECURITY CLASSIFICATION OF: The goal of this project was to enable hardware-based security techniques on future microprocessors in a way that they... microprocessors in a way that they can be added and updated after fabrication, similar to software, while maintaining the efficiency and the security of...Progress The goal of this project was to enable hardware-based security techniques on future microprocessors in a way that they can be added and

What Added Value Does Peer Support Bring? Insights from Principals and Teachers on the Utility and Challenges of a School-Based Mentoring Programme

ERIC Educational Resources Information Center

Brady, Bernadine; Dolan, Pat; Canavan, John

2014-01-01

Over the past decade, there has been greater attention placed on the potential value of peer support models, particularly in school contexts. This paper uses the case study of an Irish school-based peer mentoring programme to identify the added value that peer led models of social support for children and young people offer in a school setting.…

Lymphoblast-derived integration-free iPSC line AD-TREM2-3 from a 74 year-old Alzheimer's disease patient expressing the TREM2 p.R47H variant.

PubMed

Martins, Soraia; Yigit, Hatice; Bohndorf, Martina; Graffmann, Nina; Fiszl, Aurelian Robert; Wruck, Wasco; Sleegers, Kristel; Van Broeckhoven, Christine; Adjaye, James

2018-06-01

Human lymphoblast cells from a male diagnosed with Alzheimer's disease (AD) expressing the TREM2 p.R47H variant were used to generate integration-free induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids harbouring OCT4, SOX2, KLF4, LIN28, L-MYC and p53 shRNA. The derived iPSC line - AD-TREM2-3 was defined as pluripotent based on (i) expression of pluripotency-associated markers (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptome of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0.940. Copyright © 2018. Published by Elsevier B.V.

[Advance directives and advance care planning].

PubMed

Vayne-Bossert, Petra; Vailloud, Christiane; Ducloux, Dominique; Matis, Caroline; Déramé, Laurence

2017-02-01

Advance directives (AD) and Advance Care Planning (ACP) are two measures a person may undertake to assure that their treatment preferences will be respected until the end of his / her life. Anticipation is based on an open and honest communication between the patient, the durable medical power of attorney and the health care professionals. ADs and ACPs are based on a person's values and beliefs that are important to his quality of life. ACP is a continuing process, initiated by health care professionals and integrated into the health care plan of a person. It should be adjusted all along the disease trajectory and favors communication and anticipation in the health care network. ADs are often a personal initiative to ensure one's wishes in relation to health issues. In Switzerland, they are based on a legal framework and their application is therefore mandatory for health care professionals.

The Plasmodium gaboni genome illuminates allelic dimorphism of immunologically important surface antigens in P. falciparum.

PubMed

Roy, Scott William

2015-12-01

In the deadly human malaria parasite Plasmodium falciparum, several major merozoite surface proteins (MSPs) show a striking pattern of allelic diversity called allelic dimorphism (AD). In AD, the vast majority of observed alleles fall into two highly divergent allelic classes, with recombinant alleles being rare or not observed, presumably due to repression by natural selection (recombination suppression, or RS). The three AD loci, merozoite surface proteins (MSPs) 1, 2, and 6, along with MSP3, which also exhibits RS among four allelic classes, can be collectively called AD/RS. The causes of AD/RS and the evolutionary history of allelic diversity at these loci remain mysterious. The few available sequences from a single closely related chimpanzee parasite, P. reichenowi, have suggested that for 3/4 loci, AD/RS is an ancient state that has been retained in P. falciparum since well before the P. falciparum-P. reichenowi ancestor. On the other hand, based on comparative sequence analysis, we recently suggested that (i) AD/RS P. falciparum loci have undergone interallelic recombination over longer evolutionary times (on the timescale of recent speciation events), and thus (ii) AD/RS may be a recent phenomenon. The recent publication of genomic sequencing efforts for P. gaboni, an outgroup to P. falciparum and P. reichenowi, allows for improved reconstruction of the evolutionary history of these loci. In this work, I report genic sequence for P. gaboni for all four AD/RS P. falciparum loci (MSP1, 2, 3, and 6). Comparison of these sequences with available P. falciparum and P. reichenowi data strengthens the evidence for interallelic recombination over the evolutionary history of these species and also strengthens the case that AD/RS at these loci is ancient. Combined with previous results, these data provide evidence that AD/RS at different loci has evolved at several different times in the evolutionary history of P. falciparum: (i) before the P. gaboni-P. falciparum divergence, for much of MSP1 and MSP3; (ii) between the P. gaboni-P. falciparum and P. reichenowi-P. falciparum divergences, for the 5' end of the AD region of MSP6 and block 3 of MSP1; (iii) near the P. reichenowi-P. falciparum divergence, for the 3' end of the AD region of MSP6; and (iv) after the P. reichenowi-P. falciparum divergence, for MSP2. Based on these results, I suggest a new hypothesis for long-term evolutionary maintenance of AD/RS by recombination within allelic groups. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhancement mechanism of the additional absorbent on the absorption of the absorbing composite using a type-based mixing rule

NASA Astrophysics Data System (ADS)

Xu, Yonggang; Yuan, Liming; Zhang, Deyuan

2016-04-01

A silicone rubber composite filled with carbonyl iron particles and four different carbonous materials (carbon black, graphite, carbon fiber or multi-walled carbon nanotubes) was prepared using a two-roller mixture. The complex permittivity and permeability were measured using a vector network analyzer at the frequency of 2-18 GHz. Then a type-based mixing rule based on the dielectric absorbent and magnetic absorbent was proposed to reveal the enhancing mechanism on the permittivity and permeability. The enforcement effect lies in the decreased percolation threshold and the changing pending parameter as the carbonous materials were added. The reflection loss (RL) result showed the added carbonous materials enhanced the absorption in the lower frequency range, the RL decrement value being about 2 dB at 4-5 GHz with a thickness of 1 mm. All the added carbonous materials reinforced the shielding effectiveness (SE) of the composites. The maximum increment value of the SE was about 3.23 dB at 0.5 mm and 4.65 dB at 1 mm, respectively. The added carbonous materials could be effective additives for enforcing the absorption and shielding property of the absorbers.

Joint association discovery and diagnosis of Alzheimer's disease by supervised heterogeneous multiview learning.

PubMed

Zhe, Shandian; Xu, Zenglin; Qi, Yuan; Yu, Peng

2014-01-01

A key step for Alzheimer's disease (AD) study is to identify associations between genetic variations and intermediate phenotypes (e.g., brain structures). At the same time, it is crucial to develop a noninvasive means for AD diagnosis. Although these two tasks-association discovery and disease diagnosis-have been treated separately by a variety of approaches, they are tightly coupled due to their common biological basis. We hypothesize that the two tasks can potentially benefit each other by a joint analysis, because (i) the association study discovers correlated biomarkers from different data sources, which may help improve diagnosis accuracy, and (ii) the disease status may help identify disease-sensitive associations between genetic variations and MRI features. Based on this hypothesis, we present a new sparse Bayesian approach for joint association study and disease diagnosis. In this approach, common latent features are extracted from different data sources based on sparse projection matrices and used to predict multiple disease severity levels based on Gaussian process ordinal regression; in return, the disease status is used to guide the discovery of relationships between the data sources. The sparse projection matrices not only reveal the associations but also select groups of biomarkers related to AD. To learn the model from data, we develop an efficient variational expectation maximization algorithm. Simulation results demonstrate that our approach achieves higher accuracy in both predicting ordinal labels and discovering associations between data sources than alternative methods. We apply our approach to an imaging genetics dataset of AD. Our joint analysis approach not only identifies meaningful and interesting associations between genetic variations, brain structures, and AD status, but also achieves significantly higher accuracy for predicting ordinal AD stages than the competing methods.

A population-based study of familial Alzheimer disease: linkage to chromosomes 14, 19, and 21.

PubMed

van Duijn, C M; Hendriks, L; Farrer, L A; Backhovens, H; Cruts, M; Wehnert, A; Hofman, A; Van Broeckhoven, C

1994-10-01

Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19, and 21 was studied in 10 families in which the disease was apparently inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD. Although in all probands the onset of AD was at or before age 65 years, the mean age at onset was after age 65 years in four families (referred to as "LOAD"). Among the six families with early-onset AD (referred to as "EOAD," i.e., mean age of onset of AD of relatives was at or before age 65 years), conclusive linkage to 14q24.3 was found in one family with a very early onset (around 47 years), while linkage to the same region was excluded in two other families. For the LOAD families, predominantly negative lod scores were obtained, and the overall lod score excluded linkage to chromosome 14. The results with markers on chromosome 19 and chromosome 21 were not conclusive for EOAD and LOAD. The findings of our study confirm genetic heterogeneity within familial EOAD.

NIA-AA Staging of Preclinical Alzheimer Disease: Discordance and Concordance of CSF and Imaging Biomarkers

PubMed Central

Vos, Stephanie J. B.; Gordon, Brian A.; Su, Yi; Visser, Pieter Jelle; Holtzman, David M.; Morris, John C.; Fagan, Anne M.; Benzinger, Tammie L. S.

2016-01-01

The National Institute of Aging and Alzheimer’s Association (NIA-AA) criteria for Alzheimer disease (AD) treat neuroimaging and cerebrospinal fluid (CSF) markers of AD pathology as if they would be interchangeable. We tested this assumption in 212 cognitively normal participants who have both neuroimaging and CSF measures of β-amyloid (CSF Aβ1-42 and PET imaging with Pittsburgh Compound B) and neuronal injury (CSF t-tau and p-tau and structural MRI) with longitudinal clinical follow-up. Participants were classified in preclinical AD Stage 1 (β-amyloidosis) or preclinical AD Stage 2+ (β-amyloidosis and neuronal injury) using the NIA-AA criteria, or in the normal or suspected non-Alzheimer pathophysiology group (SNAP; neuronal injury without β-amyloidosis). At baseline, 21% of participants had preclinical AD based on CSF and 28% based upon neuroimaging. Between modalities, staging was concordant in only 47% of participants. Disagreement resulted from low concordance between biomarkers of neuronal injury. Still, individuals in Stage 2+ using either criterion had an increased risk for clinical decline. This highlights the heterogeneity of the definition of neuronal injury, and has important implications for clinical trials utilizing biomarkers for enrollment or as surrogate endpoint measures. PMID:27318129

GUIDELINES OF CARE FOR THE MANAGEMENT OF ATOPIC DERMATITIS

PubMed Central

Sidbury, Robert; Davis, Dawn M.; Cohen, David E.; Cordoro, Kelly M.; Berger, Timothy G.; Bergman, James N.; Chamlin, Sarah L.; Cooper, Kevin D.; Feldman, Steven R.; Hanifin, Jon M.; Krol, Alfons; Margolis, David J.; Paller, Amy S.; Schwarzenberger, Kathryn; Silverman, Robert A.; Simpson, Eric L.; Tom, Wynnis L.; Williams, Hywel C.; Elmets, Craig A.; Block, Julie; Harrod, Christopher G.; Begolka, Wendy Smith; Eichenfield, Lawrence F.

2014-01-01

Atopic dermatitis (AD) is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2-3% of adults. This guideline addresses important clinical questions that arise in AD management and care, providing recommendations based on the available evidence. In this third of four sections, treatment of AD with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option. PMID:24813298

A Secure and Privacy-Preserving Targeted Ad-System

NASA Astrophysics Data System (ADS)

Androulaki, Elli; Bellovin, Steven M.

Thanks to its low product-promotion cost and its efficiency, targeted online advertising has become very popular. Unfortunately, being profile-based, online advertising methods violate consumers' privacy, which has engendered resistance to the ads. However, protecting privacy through anonymity seems to encourage click-fraud. In this paper, we define consumer's privacy and present a privacy-preserving, targeted ad system (PPOAd) which is resistant towards click fraud. Our scheme is structured to provide financial incentives to all entities involved.

Value management program: performance, quantification, and presentation of imaging value-added actions.

PubMed

Patel, Samir

2015-03-01

Health care is in a state of transition, shifting from volume-based success to value-based success. Hospital executives and referring physicians often do not understand the total value a radiology group provides. A template for easy, cost-effective implementation in clinical practice for most radiology groups to demonstrate the value they provide to their clients (patients, physicians, health care executives) has not been well described. A value management program was developed to document all of the value-added activities performed by on-site radiologists, quantify them in terms of time spent on each activity (investment), and present the benefits to internal and external stakeholders (outcomes). The radiology value-added matrix is the platform from which value-added activities are categorized and synthesized into a template for defining investments and outcomes. The value management program was first implemented systemwide in 2013. Across all serviced locations, 9,931.75 hours were invested. An annual executive summary report template demonstrating outcomes is given to clients. The mean and median individual value-added hours per radiologist were 134.52 and 113.33, respectively. If this program were extrapolated to the entire field of radiology, approximately 30,000 radiologists, this would have resulted in 10,641,161 uncompensated value-added hours documented in 2013, with an estimated economic value of $2.21 billion. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Alzheimer disease research in the 21st century: past and current failures, new perspectives and funding priorities.

PubMed

Pistollato, Francesca; Ohayon, Elan L; Lam, Ann; Langley, Gillian R; Novak, Thomas J; Pamies, David; Perry, George; Trushina, Eugenia; Williams, Robin S B; Roher, Alex E; Hartung, Thomas; Harnad, Stevan; Barnard, Neal; Morris, Martha Clare; Lai, Mei-Chun; Merkley, Ryan; Chandrasekera, P Charukeshi

2016-06-28

Much of Alzheimer disease (AD) research has been traditionally based on the use of animals, which have been extensively applied in an effort to both improve our understanding of the pathophysiological mechanisms of the disease and to test novel therapeutic approaches. However, decades of such research have not effectively translated into substantial therapeutic success for human patients. Here we critically discuss these issues in order to determine how existing human-based methods can be applied to study AD pathology and develop novel therapeutics. These methods, which include patient-derived cells, computational analysis and models, together with large-scale epidemiological studies represent novel and exciting tools to enhance and forward AD research. In particular, these methods are helping advance AD research by contributing multifactorial and multidimensional perspectives, especially considering the crucial role played by lifestyle risk factors in the determination of AD risk. In addition to research techniques, we also consider related pitfalls and flaws in the current research funding system. Conversely, we identify encouraging new trends in research and government policy. In light of these new research directions, we provide recommendations regarding prioritization of research funding. The goal of this document is to stimulate scientific and public discussion on the need to explore new avenues in AD research, considering outcome and ethics as core principles to reliably judge traditional research efforts and eventually undertake new research strategies.

Nurse Value-Added and Patient Outcomes in Acute Care

PubMed Central

Yakusheva, Olga; Lindrooth, Richard; Weiss, Marianne

2014-01-01

Objective The aims of the study were to (1) estimate the relative nurse effectiveness, or individual nurse value-added (NVA), to patients’ clinical condition change during hospitalization; (2) examine nurse characteristics contributing to NVA; and (3) estimate the contribution of value-added nursing care to patient outcomes. Data Sources/Study Setting Electronic data on 1,203 staff nurses matched with 7,318 adult medical–surgical patients discharged between July 1, 2011 and December 31, 2011 from an urban Magnet-designated, 854-bed teaching hospital. Study Design Retrospective observational longitudinal analysis using a covariate-adjustment value-added model with nurse fixed effects. Data Collection/Extraction Methods Data were extracted from the study hospital's electronic patient records and human resources databases. Principal Findings Nurse effects were jointly significant and explained 7.9 percent of variance in patient clinical condition change during hospitalization. NVA was positively associated with having a baccalaureate degree or higher (0.55, p = .04) and expertise level (0.66, p = .03). NVA contributed to patient outcomes of shorter length of stay and lower costs. Conclusions Nurses differ in their value-added to patient outcomes. The ability to measure individual nurse relative value-added opens the possibility for development of performance metrics, performance-based rankings, and merit-based salary schemes to improve patient outcomes and reduce costs. PMID:25256089

Anti-tau oligomers passive vaccination for the treatment of Alzheimer disease.

PubMed

Kayed, Rakez

2010-11-01

The aggregation and accumulation of the microtubule-associated protein (Tau) is a pathological hallmark of Alzheimer's disease (AD) and many neurodegenerative diseases. Despite the poor correlation between neurofirillary tangles (NFTs) and disease progression, and evidence showing, that neuronal loss in AD actually precedes NFTs formation research until recently focused on them and other large meta-stable inclusions composed of aggregated hyperphosphorylated tau protein. Lately, the significance and toxicity of NFTs has been challenged and new aggregated tau entity has emerged as the true pathogenic species in tauopathies and a possible mediator of Aβ toxicity in AD. Tau intermediate aggregate (tau oligomers; aggregates of an intermediate that is between monomers and NFTs in size) can cause neurodegeneration and memory impairment in the absence of Aβ. This exciting body of evidence includes results from human brain samples, transgenic mouse and cell-based studies. Despite extensive efforts to develop a safe and efficacious vaccine for AD using Aβ peptide as an immunogen in active vaccination approaches or anti Aβ antibodies for passive vaccination, success has been modest. Nonetheless, these studies have produced a wealth of fundamental knowledge that has potential to application to the development of a tau-based immunotherapy. Herein, I discuss the evidence supporting the critical role of tau oligomers in AD, the potential and challenges for targeting them by immunotherapy as a novel approach for AD treatment.

Alzheimer disease research in the 21st century: past and current failures, new perspectives and funding priorities

PubMed Central

Pistollato, Francesca; Ohayon, Elan L.; Lam, Ann; Langley, Gillian R.; Novak, Thomas J.; Pamies, David; Perry, George; Trushina, Eugenia; Williams, Robin S.B.; Roher, Alex E.; Hartung, Thomas; Harnad, Stevan; Barnard, Neal; Morris, Martha Clare; Lai, Mei-Chun; Merkley, Ryan; Chandrasekera, P. Charukeshi

2016-01-01

Much of Alzheimer disease (AD) research has been traditionally based on the use of animals, which have been extensively applied in an effort to both improve our understanding of the pathophysiological mechanisms of the disease and to test novel therapeutic approaches. However, decades of such research have not effectively translated into substantial therapeutic success for human patients. Here we critically discuss these issues in order to determine how existing human-based methods can be applied to study AD pathology and develop novel therapeutics. These methods, which include patient-derived cells, computational analysis and models, together with large-scale epidemiological studies represent novel and exciting tools to enhance and forward AD research. In particular, these methods are helping advance AD research by contributing multifactorial and multidimensional perspectives, especially considering the crucial role played by lifestyle risk factors in the determination of AD risk. In addition to research techniques, we also consider related pitfalls and flaws in the current research funding system. Conversely, we identify encouraging new trends in research and government policy. In light of these new research directions, we provide recommendations regarding prioritization of research funding. The goal of this document is to stimulate scientific and public discussion on the need to explore new avenues in AD research, considering outcome and ethics as core principles to reliably judge traditional research efforts and eventually undertake new research strategies. PMID:27229915

A 2000 year varve-based climate record from the central Brooks Range, Alaska

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bird, BW; Abbott, MB; Finney, BP

Varved minerogenic sediments from glacial-fed Blue Lake, northern Alaska, are used to investigate late Holocene climate variability. Varve-thickness measurements track summer temperature recorded at Atigun Pass, located 41 km east at a similar elevation (r (2) = 0.31, P = 0.08). Results indicate that climate in the Brooks Range from 10 to 730 AD (varve year) was warm with precipitation inferred to be higher than during the twentieth century. The varvetemperature relationship for this period was likely compromised and not used in our temperature reconstruction because the glacier was greatly reduced, or absent, exposing sub-glacial sediments to erosion from enhancedmore » precipitation. Varve-inferred summer temperatures and precipitation decreased after 730 AD, averaging 0.4A degrees C above the last millennial average (LMA = 4.2A degrees C) from 730 to 850 AD, and 0.1A degrees C above the LMA from 850 to 980 AD. Cooling culminated between 980 and 1030 AD with temperatures 0.7A degrees C below the LMA. Varve-inferred summer temperatures increased between 1030 and 1620 AD to the LMA, though the period between 1260 and 1350 AD was 0.2A degrees C below the LMA. Although there is no equivalent to the European Medieval Warm Period in the Blue Lake record, two warm intervals occurred from 1350 to 1450 AD and 1500 to 1620 AD (0.4 and 0.3A degrees C above the LMA, respectively). During the Little Ice Age (LIA; 1620 to 1880 AD), inferred summer temperature averaged 0.2A degrees C below the LMA. After 1880 AD, inferred summer temperature increased to 0.8A degrees C above the LMA, glaciers retreated, but aridity persisted based on a number of regional paleoclimate records. Despite warming and glacial retreat, varve thicknesses have not achieved pre-730 AD levels. This reflects limited sediment availability and transport due to a less extensive retreat compared to the first millennium, and continued relative aridity. Overall, the Blue Lake record is similar to varve records from the eastern Canadian Arctic that document a cool LIA and twentieth century warming. However, the occurrence and timing of events, such as the LIA and Medieval Warm Period, varies considerably among records, suggesting heterogeneous climatic patterns across the North American Arctic.« less

Active-Pixel Image Sensor With Analog-To-Digital Converters

NASA Technical Reports Server (NTRS)

Fossum, Eric R.; Mendis, Sunetra K.; Pain, Bedabrata; Nixon, Robert H.

1995-01-01

Proposed single-chip integrated-circuit image sensor contains 128 x 128 array of active pixel sensors at 50-micrometer pitch. Output terminals of all pixels in each given column connected to analog-to-digital (A/D) converter located at bottom of column. Pixels scanned in semiparallel fashion, one row at time; during time allocated to scanning row, outputs of all active pixel sensors in row fed to respective A/D converters. Design of chip based on complementary metal oxide semiconductor (CMOS) technology, and individual circuit elements fabricated according to 2-micrometer CMOS design rules. Active pixel sensors designed to operate at video rate of 30 frames/second, even at low light levels. A/D scheme based on first-order Sigma-Delta modulation.

Harmonised investigation of the occurrence of human enteric viruses in the leafy green vegetable supply chain in three European countries.

PubMed

Kokkinos, P; Kozyra, I; Lazic, S; Bouwknegt, M; Rutjes, S; Willems, K; Moloney, R; de Roda Husman, A M; Kaupke, A; Legaki, E; D'Agostino, M; Cook, N; Rzeżutka, A; Petrovic, T; Vantarakis, A

2012-12-01

Numerous outbreaks have been attributed to the consumption of raw or minimally processed leafy green vegetables contaminated with enteric viral pathogens. The aim of the present study was an integrated virological monitoring of the salad vegetables supply chain in Europe, from production, processing and point-of-sale. Samples were collected and analysed in Greece, Serbia and Poland, from 'general' and 'ad hoc' sampling points, which were perceived as critical points for virus contamination. General sampling points were identified through the analysis of background information questionnaires based on HACCP audit principles, and they were sampled during each sampling occasion where as-ad hoc sampling points were identified during food safety fact-finding visits and samples were only collected during the fact-finding visits. Human (hAdV) and porcine (pAdV) adenovirus, hepatitis A (HAV) and E (HEV) virus, norovirus GI and GII (NoV) and bovine polyomavirus (bPyV) were detected by means of real-time (RT-) PCR-based protocols. General samples were positive for hAdV, pAdV, HAV, HEV, NoV GI, NoV GII and bPyV at 20.09 % (134/667), 5.53 % (13/235), 1.32 % (4/304), 3.42 % (5/146), 2 % (6/299), 2.95 % (8/271) and 0.82 % (2/245), respectively. Ad hoc samples were positive for hAdV, pAdV, bPyV and NoV GI at 9 % (3/33), 9 % (2/22), 4.54 % (1/22) and 7.14 % (1/14), respectively. These results demonstrate the existence of viral contamination routes from human and animal sources to the salad vegetable supply chain and more specifically indicate the potential for public health risks due to the virus contamination of leafy green vegetables at primary production.

Using Individualized Brain Network for Analyzing Structural Covariance of the Cerebral Cortex in Alzheimer's Patients.

PubMed

Kim, Hee-Jong; Shin, Jeong-Hyeon; Han, Cheol E; Kim, Hee Jin; Na, Duk L; Seo, Sang Won; Seong, Joon-Kyung

2016-01-01

Cortical thinning patterns in Alzheimer's disease (AD) have been widely reported through conventional regional analysis. In addition, the coordinated variance of cortical thickness in different brain regions has been investigated both at the individual and group network levels. In this study, we aim to investigate network architectural characteristics of a structural covariance network (SCN) in AD, and further to show that the structural covariance connectivity becomes disorganized across the brain regions in AD, while the normal control (NC) subjects maintain more clustered and consistent coordination in cortical atrophy variations. We generated SCNs directly from T1-weighted MR images of individual patients using surface-based cortical thickness data, with structural connectivity defined as similarity in cortical thickness within different brain regions. Individual SCNs were constructed using morphometric data from the Samsung Medical Center (SMC) dataset. The structural covariance connectivity showed higher clustering than randomly generated networks, as well as similar minimum path lengths, indicating that the SCNs are "small world." There were significant difference between NC and AD group in characteristic path lengths (z = -2.97, p < 0.01) and small-worldness values (z = 4.05, p < 0.01). Clustering coefficients in AD was smaller than that of NC but there was no significant difference (z = 1.81, not significant). We further observed that the AD patients had significantly disrupted structural connectivity. We also show that the coordinated variance of cortical thickness is distributed more randomly from one region to other regions in AD patients when compared to NC subjects. Our proposed SCN may provide surface-based measures for understanding interaction between two brain regions with co-atrophy of the cerebral cortex due to normal aging or AD. We applied our method to the AD Neuroimaging Initiative (ADNI) data to show consistency in results with the SMC dataset.

[BACE1 inhibitors for the treatment of Alzheimer disease].

PubMed

Tomita, Taisuke

2016-03-01

β-Site amyloid precursor protein cleaving enzyme 1 (BACEl) is the enzyme required for the production of the amyloid-β peptide(Aβ), which is associated with Alzheimer disease (AD). BACEl has emerged as a prime molecular target for reducing the brain Aβ levels. Recently, several BACEl inhibitors have been developed in clinical trials to test the efficacy in AD patients and individuals with prodromal AD. However, identification of BACE1 substrates and phenotypes of Bace1 knockout mice have raised concerns regarding potential mechanism-based adverse effects. This review summarizes the current status of the development of BACE1 inhibitors and the evaluation of their therapeutic potential against AD.

Constructing an explicit AdS/CFT correspondence with Cartan geometry

NASA Astrophysics Data System (ADS)

Hazboun, Jeffrey S.

2018-04-01

An explicit AdS/CFT correspondence is shown for the Lie group SO (4 , 2). The Lie symmetry structures allow for the construction of two physical theories through the tools of Cartan geometry. One is a gravitational theory that has anti-de Sitter symmetry. The other is also a gravitational theory but is conformally symmetric and lives on 8-dimensional biconformal space. These "extra" four dimensions have the degrees of freedom used to construct a Yang-Mills theory. The two theories, based on AdS or conformal symmetry, have a natural correspondence in the context of their Lie algebras alone where neither SUSY, nor holography, is necessary.

History and Experience: A Survey of Traditional Chinese Medicine Treatment for Alzheimer's Disease

PubMed Central

Liu, Ping; Kong, Mingwang; Yuan, Shihe; Liu, Junfeng; Wang, Ping

2014-01-01

Traditional Chinese medicine (TCM) is practiced in the Chinese health care system for more than 2,000 years. In recent years, herbal medicines, which are used to treat Alzheimer's disease (AD) in China based on TCM or modern pharmacological theories have attracted considerable attention. In this paper, we discuss etiology and pathogenesis of AD, TCM therapy, and herbal extracts for the treatment of AD. There is evidence to suggest that TCM therapy may offer certain complementary cognitive benefits for the treatment of AD. Chinese herb may have advantages with multiple target regulation compared with the single-target antagonist in view of TCM. PMID:24624220

Managing emergency department overcrowding via ambulance diversion: a discrete event simulation model.

PubMed

Lin, Chih-Hao; Kao, Chung-Yao; Huang, Chong-Ye

2015-01-01

Ambulance diversion (AD) is considered one of the possible solutions to relieve emergency department (ED) overcrowding. Study of the effectiveness of various AD strategies is prerequisite for policy-making. Our aim is to develop a tool that quantitatively evaluates the effectiveness of various AD strategies. A simulation model and a computer simulation program were developed. Three sets of simulations were executed to evaluate AD initiating criteria, patient-blocking rules, and AD intervals, respectively. The crowdedness index, the patient waiting time for service, and the percentage of adverse patients were assessed to determine the effect of various AD policies. Simulation results suggest that, in a certain setting, the best timing for implementing AD is when the crowdedness index reaches the critical value, 1.0 - an indicator that ED is operating at its maximal capacity. The strategy to divert all patients transported by ambulance is more effective than to divert either high-acuity patients only or low-acuity patients only. Given a total allowable AD duration, implementing AD multiple times with short intervals generally has better effect than having a single AD with maximal allowable duration. An input-throughput-output simulation model is proposed for simulating ED operation. Effectiveness of several AD strategies on relieving ED overcrowding was assessed via computer simulations based on this model. By appropriate parameter settings, the model can represent medical resource providers of different scales. It is also feasible to expand the simulations to evaluate the effect of AD strategies on a community basis. The results may offer insights for making effective AD policies. Copyright © 2012. Published by Elsevier B.V.

47 CFR 1.1404 - Complaint.

Code of Federal Regulations, 2010 CFR

2010-10-01

... telecommunications carriers for non-recurring costs. (2) Data and information should be based upon historical or... upon historical or original cost methodology, insofar as possible. Data should be derived from ARMIS...) through (n) and adding new paragraphs (g)(12) and (h) through (j). The added text contains information...

Research of Ad Hoc Networks Access Algorithm

NASA Astrophysics Data System (ADS)

Xiang, Ma

With the continuous development of mobile communication technology, Ad Hoc access network has become a hot research, Ad Hoc access network nodes can be used to expand capacity of multi-hop communication range of mobile communication system, even business adjacent to the community, improve edge data rates. When the ad hoc network is the access network of the internet, the gateway discovery protocol is very important to choose the most appropriate gateway to guarantee the connectivity between ad hoc network and IP based fixed networks. The paper proposes a QoS gateway discovery protocol which uses the time delay and stable route to the gateway selection conditions. And according to the gateway discovery protocol, it also proposes a fast handover scheme which can decrease the handover time and improve the handover efficiency.

High dietary fructose intake: Sweet or bitter life?

PubMed

Collino, Massimo

2011-06-15

Epidemiological data show that the consumption of added sugars as ingredients in processed or prepared foods and caloric beverages has dramatically increased. Fructose and fructose-based sweeteners are the most commonly added sugars and high-fructose corn syrup (HFCS-55: 55% fructose, 42% glucose and 3% higher saccharides) accounts for over 40% of all added caloric sweeteners. Concerns regarding the health risk of added sugar follow the demonstration that the consumption of foods and beverages high in sugars is associated with an increased prevalence of obesity, insulin resistance, dyslipidemia and, more recently, ischemic heart and kidney diseases. The molecular mechanism(s) underlying the detrimental effects of sugar are not completely understood and their elucidation is critical to provide new insights on the health risk of fructose-based sweeteners. A better understanding of the key role of fructose overconsumption in the development of metabolic disorders may contribute to planning new strategies for preventing deleterious dietary behaviors from becoming established and, thus, curbing the rise in the number of insulin-resistant, obese and diabetic populations worldwide.

Mild hypercholesterolemia, normal plasma triglycerides, and normal glucose levels across dementia staging in Alzheimer's disease: a clinical setting-based retrospective study.

PubMed

Ramdane, Said; Daoudi-Gueddah, Doria

2011-08-01

We examined retrospectively the concurrent relationships between fasting plasma total cholesterol, triglycerides, and glucose levels, and Alzheimer's disease (AD), in a clinical setting-based study. Total cholesterol level was higher in patients with AD compared to elderly controls; triglycerides or glucose levels did not significantly differ between the 2 groups. Respective plotted trajectories of change in cholesterol level across age were fairly parallel. No significant difference in total cholesterol levels was recorded between patients with AD classified by the Clinical Dementia Rating (CDR) score subgroups. These results suggest that patients with AD have relative mild total hypercholesterolemia, normal triglyceridemia, and normal fasting plasma glucose level. Mild total hypercholesterolemia seems to be permanent across age, and across dementia severity staging, and fairly parallels the trajectory of age-related change in total cholesterolemia of healthy controls. We speculate that these biochemical parameters pattern may be present long before-a decade at least-the symptomatic onset of the disease.

Pathogenesis of Alzheimer disease: role of oxidative stress, amyloid-β peptides, systemic ammonia and erythrocyte energy metabolism.

PubMed

Kosenko, Elena A; Solomadin, Iliya N; Tikhonova, Lyudmila A; Reddy, V Prakash; Aliev, Gjumrakch; Kaminsky, Yury G

2014-02-01

Aβ exerts prooxidant or antioxidant effects based on the metal ion concentrations that it sequesters from the cytosol; at low metal ion concentrations, it is an antioxidant, whereas at relatively higher concentration it is a prooxidant. Thus Alzheimer disease (AD) treatment strategies based solely on the amyloid-β clearance should be re-examined in light of the vast accumulating evidence that increased oxidative stress in the human brains is the key causative factor for AD. Accumulating evidence indicates that the reduced brain glucose availability and brain hypoxia, due to the relatively lower concentration of ATP and 2,3-diphosphoglycerate, may be associated with increased concentration of endogenous ammonia, a potential neurotoxin in the AD brains. In this review, we summarize the progress in this area, and present some of our ongoing research activities with regard to brain Amyloid-β, systemic ammonia, erythrocyte energy metabolism and the role of 2,3-diphosphoglycerate in AD pathogenesis.

Fisetin Reduces the Impact of Aging on Behavior and Physiology in the Rapidly Aging SAMP8 Mouse.

PubMed

Currais, Antonio; Farrokhi, Catherine; Dargusch, Richard; Armando, Aaron; Quehenberger, Oswald; Schubert, David; Maher, Pamela

2018-03-02

Alzheimer's disease (AD) is rarely addressed in the context of aging even though there is an overlap in pathology. We previously used a phenotypic screening platform based on old age-associated brain toxicities to identify the flavonol fisetin as a potential therapeutic for AD and other age-related neurodegenerative diseases. Based on earlier results with fisetin in transgenic AD mice, we hypothesized that fisetin would be effective against brain aging and cognitive dysfunction in rapidly aging senescence-accelerated prone 8 (SAMP8) mice, a model for sporadic AD and dementia. An integrative approach was used to correlate protein expression and metabolite levels in the brain with cognition. It was found that fisetin reduced cognitive deficits in old SAMP8 mice while restoring multiple markers associated with impaired synaptic function, stress, and inflammation. These results provide further evidence for the potential benefits of fisetin for the treatment of age-related neurodegenerative diseases.

SPECTRAL GRAPH THEORY AND GRAPH ENERGY METRICS SHOW EVIDENCE FOR THE ALZHEIMER’S DISEASE DISCONNECTION SYNDROME IN APOE-4 RISK GENE CARRIERS

PubMed Central

Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Hibar, Derrek P.; Nir, Talia M.; Jack, Clifford R.; Weiner, Michael W.; Bernstein, Matt A.; Thompson, Paul M.

2015-01-01

Our understanding of network breakdown in Alzheimer’s disease (AD) is likely to be enhanced through advanced mathematical descriptors. Here, we applied spectral graph theory to provide novel metrics of structural connectivity based on 3-Tesla diffusion weighted images in 42 AD patients and 50 healthy controls. We reconstructed connectivity networks using whole-brain tractography and examined, for the first time here, cortical disconnection based on the graph energy and spectrum. We further assessed supporting metrics - link density and nodal strength - to better interpret our results. Metrics were analyzed in relation to the well-known APOE-4 genetic risk factor for late-onset AD. The number of disconnected cortical regions increased with the number of copies of the APOE-4 risk gene in people with AD. Each additional copy of the APOE-4 risk gene may lead to more dysfunctional networks with weakened or abnormal connections, providing evidence for the previously hypothesized “disconnection syndrome”. PMID:26413205

UMDR: Multi-Path Routing Protocol for Underwater Ad Hoc Networks with Directional Antenna

NASA Astrophysics Data System (ADS)

Yang, Jianmin; Liu, Songzuo; Liu, Qipei; Qiao, Gang

2018-01-01

This paper presents a new routing scheme for underwater ad hoc networks based on directional antennas. Ad hoc networks with directional antennas have become a hot research topic because of space reuse may increase networks capacity. At present, researchers have applied traditional self-organizing routing protocols (such as DSR, AODV) [1] [2] on this type of networks, and the routing scheme is based on the shortest path metric. However, such routing schemes often suffer from long transmission delays and frequent link fragmentation along the intermediate nodes of the selected route. This is caused by a unique feature of directional transmission, often called as “deafness”. In this paper, we take a different approach to explore the advantages of space reuse through multipath routing. This paper introduces the validity of the conventional routing scheme in underwater ad hoc networks with directional antennas, and presents a special design of multipath routing algorithm for directional transmission. The experimental results show a significant performance improvement in throughput and latency.

The ADS All Sky Survey: footprints of astronomy literature, in the sky

NASA Astrophysics Data System (ADS)

Pepe, Alberto; Goodman, A. A.; Muench, A. A.; Seamless Astronomy Group at the CfA

2014-01-01

The ADS All-Sky Survey (ADSASS) aims to transform the NASA Astrophysics Data System (ADS), widely known for its unrivaled value as a literature resource for astronomers, into a data resource. The ADS is not a data repository per se, but it implicitly contains valuable holdings of astronomical data, in the form of images, tables and object references contained within articles. The objective of the ADSASS effort is to extract these data and make them discoverable and available through existing data viewers. In this talk, the ADSASS viewer - http://adsass.org/ - will be presented: a sky heatmap of astronomy articles based on the celestial objects they reference. The ADSASS viewer is as an innovative research and visual search tool for it allows users to explore astronomical literature based on celestial location, rather than keyword string. The ADSASS is a NASA-funded initiative carried out by the Seamless Astronomy Group at the Harvard-Smithsonian Center for Astrophysics.

SPECTRAL GRAPH THEORY AND GRAPH ENERGY METRICS SHOW EVIDENCE FOR THE ALZHEIMER'S DISEASE DISCONNECTION SYNDROME IN APOE-4 RISK GENE CARRIERS.

PubMed

Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Hibar, Derrek P; Nir, Talia M; Jack, Clifford R; Weiner, Michael W; Bernstein, Matt A; Thompson, Paul M

2015-04-01

Our understanding of network breakdown in Alzheimer's disease (AD) is likely to be enhanced through advanced mathematical descriptors. Here, we applied spectral graph theory to provide novel metrics of structural connectivity based on 3-Tesla diffusion weighted images in 42 AD patients and 50 healthy controls. We reconstructed connectivity networks using whole-brain tractography and examined, for the first time here, cortical disconnection based on the graph energy and spectrum. We further assessed supporting metrics - link density and nodal strength - to better interpret our results. Metrics were analyzed in relation to the well-known APOE -4 genetic risk factor for late-onset AD. The number of disconnected cortical regions increased with the number of copies of the APOE -4 risk gene in people with AD. Each additional copy of the APOE -4 risk gene may lead to more dysfunctional networks with weakened or abnormal connections, providing evidence for the previously hypothesized "disconnection syndrome".

Recent progress in the development of solid catalysts for biomass conversion into high value-added chemicals.

PubMed

Hara, Michikazu; Nakajima, Kiyotaka; Kamata, Keigo

2015-06-01

In recent decades, the substitution of non-renewable fossil resources by renewable biomass as a sustainable feedstock has been extensively investigated for the manufacture of high value-added products such as biofuels, commodity chemicals, and new bio-based materials such as bioplastics. Numerous solid catalyst systems for the effective conversion of biomass feedstocks into value-added chemicals and fuels have been developed. Solid catalysts are classified into four main groups with respect to their structures and substrate activation properties: (a) micro- and mesoporous materials, (b) metal oxides, (c) supported metal catalysts, and (d) sulfonated polymers. This review article focuses on the activation of substrates and/or reagents on the basis of groups (a)-(d), and the corresponding reaction mechanisms. In addition, recent progress in chemocatalytic processes for the production of five industrially important products (5-hydroxymethylfurfural, lactic acid, glyceraldehyde, 1,3-dihydroxyacetone, and furan-2,5-dicarboxylic acid) as bio-based plastic monomers and their intermediates is comprehensively summarized.

Batch anaerobic digestion of synthetic military base food waste and cardboard mixtures.

PubMed

Asato, Caitlin M; Gonzalez-Estrella, Jorge; Jerke, Amber C; Bang, Sookie S; Stone, James J; Gilcrease, Patrick C

2016-09-01

Austere US military bases typically dispose of solid wastes, including large fractions of food waste (FW) and corrugated cardboard (CCB), by open dumping, landfilling, or burning. Anaerobic digestion (AD) offers an opportunity to reduce pollution and recover useful energy. This study aimed to evaluate the rates and yields of AD for FW-CCB mixtures. Batch AD was analyzed at substrate concentrations of 1-50g total chemical oxygen demand (COD)L(-1) using response surface methodology. At low concentrations, higher proportions of FW were correlated with faster specific methanogenic activities and greater final methane yields; however, concentrations of FW ⩾18.75gCODL(-1) caused inhibition. Digestion of mixtures with ⩾75% CCB occurred slowly but achieved methane yields >70%. Greater shifts in microbial communities were observed at higher substrate concentrations. Statistical models of methane yield and specific methanogenic activity indicated that FW and CCB exhibited no considerable interactions as substrates for AD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recent progress in the development of solid catalysts for biomass conversion into high value-added chemicals

NASA Astrophysics Data System (ADS)

Hara, Michikazu; Nakajima, Kiyotaka; Kamata, Keigo

2015-06-01

In recent decades, the substitution of non-renewable fossil resources by renewable biomass as a sustainable feedstock has been extensively investigated for the manufacture of high value-added products such as biofuels, commodity chemicals, and new bio-based materials such as bioplastics. Numerous solid catalyst systems for the effective conversion of biomass feedstocks into value-added chemicals and fuels have been developed. Solid catalysts are classified into four main groups with respect to their structures and substrate activation properties: (a) micro- and mesoporous materials, (b) metal oxides, (c) supported metal catalysts, and (d) sulfonated polymers. This review article focuses on the activation of substrates and/or reagents on the basis of groups (a)-(d), and the corresponding reaction mechanisms. In addition, recent progress in chemocatalytic processes for the production of five industrially important products (5-hydroxymethylfurfural, lactic acid, glyceraldehyde, 1,3-dihydroxyacetone, and furan-2,5-dicarboxylic acid) as bio-based plastic monomers and their intermediates is comprehensively summarized.

Cost-effectiveness of sitagliptin-based treatment regimens in European patients with type 2 diabetes and haemoglobin A1c above target on metformin monotherapy.

PubMed

Schwarz, B; Gouveia, M; Chen, J; Nocea, G; Jameson, K; Cook, J; Krishnarajah, G; Alemao, E; Yin, D; Sintonen, H

2008-06-01

Sitagliptin is a novel oral incretin enhancer that acts by inhibiting the dipeptidyl peptidase 4 enzyme and is indicated in Europe as a treatment adjunct to metformin (MF), sulphonylurea (SU), MF plus SU and diet and exercise, in the management of type 2 diabetes mellitus. The objective of the current analysis was to evaluate the cost-effectiveness of adding sitagliptin to the regimens of patients with haemoglobin A1c (HbA1C) above the International Diabetes Federation goal (6.5%) while on MF in six European countries: Austria, Finland, Portugal, Scotland (United Kingdom), Spain and Sweden. A discrete event simulation model, which employed the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model risk equations for predicting risks of diabetes-related complication, was used. Lifetime costs and benefits were projected for alternative treatment strategies of adding sitagliptin, compared with adding rosiglitazone or a SU to MF in patients not at HbA1C goal on MF monotherapy. Changes in HbA1C as well as side effects associated with these different treatment strategies were based on clinical trial data. Mean baseline values from local epidemiologic studies involving patients with type 2 diabetes not at HbA1C goal on MF monotherapy were included in the current analysis. Costs of medications, side effects and direct costs of diabetes-related complications were based on country-specific data. UKPDS-based disutility weights associated with diabetes complications were incorporated. Disutilities associated with medication side effects were based on published data. All future costs and benefits were discounted according to local guidelines on cost-effectiveness analysis. One-way sensitivity analyses were conducted by varying key input parameters. The discounted incremental cost-effectiveness ratios (ICER) associated with the addition of sitagliptin to MF, compared with adding rosiglitazone, in the different countries analysed ranged from treatment with sitagliptin being dominant (cost saving with improved health outcome) to its being cost-effective [4,766 euros per quality-adjusted life year (QALY)]. Treatment with sitagliptin added to MF was cost-effective compared with adding a SU, with discounted ICER values ranging from 5949 euros/QALY to 20,350 euros/QALY across countries. Sensitivity analyses showed that these results were robust to changes in input parameters, including clinical efficacy, costs and utility weights for both diabetes-related complications and hypoglycaemia. Compared with adding rosiglitazone or a SU to MF, adding sitagliptin to MF is projected to be either cost saving or cost-effective for patients with type 2 diabetes who are not at HbA1C goal on MF.

Long term care staff beliefs about evidence based practices for the management of dementia and agitation.

PubMed

Ayalon, Liat; Arean, Patricia; Bornfeld, Heather; Beard, Renee

2009-02-01

Despite a growing literature on effective interventions for Alzheimer's disease (AD) and agitation, the management of these conditions in long term care (LTC) often is inadequate. The goals of the present study were: (a) to evaluate existing beliefs about evidence based practices (EBP) for the management of Alzheimer's disease and agitation among LTC staff; and (b) to evaluate the contribution of demographic and attitudinal variables to LTC staff beliefs about these EBP. A cross sectional study of 371 LTC staff members completed an EBP questionnaire, a short demographic questionnaire, and an attitudinal questionnaire about AD and agitation. Paraprofessional caregivers, those of lower educational level, and ethnic minorities were more likely to be in disagreement with the EBP views examined in this study. Those in disagreement with the EBP views also reported a preference towards not working with residents with AD and agitation and a sense of helplessness associated with such work. Disagreement with EBP views was associated with both normalization and stigmatization of AD and agitation. Paraprofessional caregivers, ethnic minorities, and people of lower educational level are most at need for educational activities about AD and neuropsychiatric symptoms. Educational efforts geared towards changing the belief system of LTC staff should target not only EBP but also information about AD and agitation as conditions that are deviant from the normal aging process, yet non-stigmatizing. It is expected that following EBP will empower staff and improve staff motivation to work with residents with AD and agitation. (c) 2008 John Wiley & Sons, Ltd.

Brain regions associated with anosognosia for memory disturbance in Alzheimer's disease: a magnetic resonance imaging study.

PubMed

Fujimoto, Hiroshi; Matsuoka, Teruyuki; Kato, Yuka; Shibata, Keisuke; Nakamura, Kaeko; Yamada, Kei; Narumoto, Jin

2017-01-01

Patients with Alzheimer's disease (AD) are frequently unaware of their cognitive symptoms and medical diagnosis. The term "anosognosia" is used to indicate a general lack of awareness of one's disease or disorder. The neural substrate underlying anosognosia in AD is unclear. Since anosognosia for memory disturbance might be an initial sign of AD, it is important to determine the neural correlates. This study was designed to investigate the characteristics and neural correlates of anosognosia for memory disturbance in patients with mild AD. The subjects were 49 patients with mild AD who participated in a retrospective cross-sectional study. None of the patients had been treated with cholinesterase inhibitors, memantine, or psychotropic drugs. All patients underwent magnetic resonance imaging (MRI). Anosognosia for memory disturbance was assessed based on the discrepancy between questionnaire scores of patients and their caregivers. Structural MRI data were analyzed to explore the association between anosognosia and brain atrophy, using a voxel-based approach. Statistical parametric mapping software was used to explore neural correlations. In image analysis, multiple regression analysis was performed to examine the relationship between anosognosia score and regional gray matter volume. Age, years of education, and total intracranial volume were entered as covariates. The anosognosia score for memory disturbance was significantly negatively correlated with gray matter volume in the left superior frontal gyrus. The left superior frontal gyrus was involved in anosognosia for memory disturbance, while the medial temporal lobe, which is usually damaged in mild AD, was not associated with anosognosia. The left superior frontal gyrus might be an important region for anosognosia in mild AD.

ADS-B within a Multi-Aircraft Simulation for Distributed Air-Ground Traffic Management

NASA Technical Reports Server (NTRS)

Barhydt, Richard; Palmer, Michael T.; Chung, William W.; Loveness, Ghyrn W.

2004-01-01

Automatic Dependent Surveillance Broadcast (ADS-B) is an enabling technology for NASA s Distributed Air-Ground Traffic Management (DAG-TM) concept. DAG-TM has the goal of significantly increasing capacity within the National Airspace System, while maintaining or improving safety. Under DAG-TM, aircraft exchange state and intent information over ADS-B with other aircraft and ground stations. This information supports various surveillance functions including conflict detection and resolution, scheduling, and conformance monitoring. To conduct more rigorous concept feasibility studies, NASA Langley Research Center s PC-based Air Traffic Operations Simulation models a 1090 MHz ADS-B communication structure, based on industry standards for message content, range, and reception probability. The current ADS-B model reflects a mature operating environment and message interference effects are limited to Mode S transponder replies and ADS-B squitters. This model was recently evaluated in a Joint DAG-TM Air/Ground Coordination Experiment with NASA Ames Research Center. Message probability of reception vs. range was lower at higher traffic levels. The highest message collision probability occurred near the meter fix serving as the confluence for two arrival streams. Even the highest traffic level encountered in the experiment was significantly less than the industry standard "LA Basin 2020" scenario. Future studies will account for Mode A and C message interference (a major effect in several industry studies) and will include Mode A and C aircraft in the simulation, thereby increasing the total traffic level. These changes will support ongoing enhancements to separation assurance functions that focus on accommodating longer ADS-B information update intervals.

Adenovirus Vector Pseudotyping in Fiber-Expressing Cell Lines: Improved Transduction of Epstein-Barr Virus-Transformed B Cells

PubMed Central

Von Seggern, Dan J.; Huang, Shuang; Fleck, Shonna Kaye; Stevenson, Susan C.; Nemerow, Glen R.

2000-01-01

While adenovirus (Ad) gene delivery vectors are useful in many gene therapy applications, their broad tropism means that they cannot be directed to a specific target cell. There are also a number of cell types involved in human disease which are not transducible with standard Ad vectors, such as Epstein-Barr virus (EBV)-transformed B lymphocytes. Adenovirus binds to host cells via the viral fiber protein, and Ad vectors have previously been retargeted by modifying the fiber gene on the viral chromosome. This requires that the modified fiber be able to bind to the cell in which the vector is grown, which prevents truly specific vector targeting. We previously reported a gene delivery system based on a fiber gene-deleted Ad type 5 (Ad5) vector (Ad5.βgal.ΔF) and packaging cells that express the viral fiber protein. Expression of different fibers in packaging cells will allow Ad retargeting without modifying the viral chromosome. Importantly, fiber proteins which can no longer bind to the producer cells can also be used. Using this approach, we generated for the first time pseudotyped Ad5.βgal.ΔF particles containing either the wild-type Ad5 fiber protein or a chimeric fiber with the receptor-binding knob domain of the Ad3 fiber. Particles equipped with the chimeric fiber bound to the Ad3 receptor rather than the coxsackievirus-adenovirus receptor protein used by Ad5. EBV-transformed B lymphocytes were infected efficiently by the Ad3-pseudotyped particles but poorly by virus containing the Ad5 fiber protein. The strategy described here represents a broadly applicable method for targeting gene delivery to specific cell types. PMID:10590124

Treadmill Running Reverses Cognitive Declines due to Alzheimer Disease.

PubMed

Cho, Jinkyung; Shin, Min-Kyoo; Kim, Donghyun; Lee, Inhwan; Kim, Shinuk; Kang, Hyunsik

2015-09-01

This study investigated the effect of treadmill running on cognitive declines in the early and advanced stages of Alzheimer disease (AD) in 3xTg-AD mice. At 4 months of age, 3xTg-AD mice (N = 24) were assigned to control (AD + CON, n = 12) or exercise (AD + EX, n = 12) group. At 24 months of age, 3xTg-AD mice (N = 16) were assigned to AD + CON (n = 8) or AD + EX (n = 8) group. The AD + EX mice were subjected to treadmill running for 12 wk. At each pathological stage, the background strain mice were included as wild-type control (WT + CON, n = 8-12). At the early stage of AD, 3xTg-AD mice had impaired short- and long-term memory based on Morris water maze along with higher cortical Aβ deposition, higher hippocampal and cortical tau pathology, and lower hippocampal and cortical PSD-95 and synaptophysin. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the tau pathology along with suppression of the decreased PSD-95 and synaptophysin in the hippocampus and cortex. At the advanced stage of AD, 3xTg-AD mice had impaired short- and long-term memory along with higher levels of Aβ deposition, soluble Aβ1-40 and Aβ1-42, tau pathology, and lower levels of brain-derived neurotrophic factor, PSD-95, and synaptophysin in the hippocampus and cortex. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the Aβ and tau pathology along with suppression of the decreased synaptic proteins and brain-derived neurotrophic factor in the hippocampus and cortex. The current findings suggest that treadmill running provides a nonpharmacological means to combat cognitive declines due to AD pathology.

Assessment of Alzheimer’s disease case–control associations using family-based methods

PubMed Central

Schjeide, Brit-Maren M.; McQueen, Matthew B.; Mullin, Kristina; DiVito, Jason; Hogan, Meghan F.; Parkinson, Michele; Hooli, Basavaraj; Lange, Christoph; Blacker, Deborah; Tanzi, Rudolph E.

2009-01-01

The genetics of Alzheimer’s disease (AD) is heterogeneous and remains only ill-defined. We have recently created a freely available and continuously updated online database (AlzGene; http://www.alzgene.org) for which we collect all published genetic association studies in AD and perform systematic meta-analyses on all polymorphisms with sufficient genotype data. In this study, we tested 27 genes (ACE, BDNF, CH25H, CHRNB2, CST3, CTSD, DAPK1, GALP, hCG2039140, IL1B, LMNA, LOC439999, LOC651924, MAPT, MTHFR, MYH13, PCK1, PGBD1, PRNP, PSEN1, SORCS1, SORL1, TF, TFAM, TNK1, GWA_14q32.13, and GWA_7p15.2), all showing significant association with AD risk in the AlzGene meta-analyses, in a large collection of family-based samples comprised of 4,180 subjects from over 1,300 pedigrees. Overall, we observe significant association with risk for AD and polymorphisms in ACE, CHRNB2, TF, and an as yet uncharacterized locus on chromosome 7p15.2 [rs1859849]. For all four loci, the association was observed with the same alleles as in the AlzGene meta-analyses. The convergence of case–control and family-based findings suggests that these loci currently represent the most promising AD gene candidates. Further fine-mapping and functional analyses are warranted to elucidate the potential biochemical mechanisms and epidemiological relevance of these genes. PMID:18830724

Frontal Lobe Function and Risk of Hip Fracture in Patient With Alzheimer Disease: An Analysis of Linked Data.

PubMed

Roh, Hyun Woong; Hong, Chang Hyung; Lee, SooJin; Lee, Yunhwan; Lee, Kang Soo; Chang, Ki Jung; Oh, Byoung Hoon; Choi, Seong Hye; Kim, Seong Yoon; Back, Joung Hwan; Chung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Son, Sang Joon

2015-11-01

To determine the association between frontal lobe function and risk of hip fracture in patients with Alzheimer disease (AD).Retrospective cohort study using multicenter hospital-based dementia registry and national health insurance claim data was done. Participants who had available data of neuropsychological test, national health insurance claim, and other covariates were included. A total of 1660 patients with AD were included based on Stroop Test results. A total of 1563 patients with AD were included based on the Controlled Oral Word Association Test (COWAT) results. Hip fracture was measured by validated identification criteria using national health insurance claim data. Frontal lobe function was measured by Stroop Test and COWAT at baseline.After adjusting for potential covariates, including cognitive function in other domains (language, verbal and nonverbal memory, and attention), the Cox proportional hazard regression analysis revealed that risk of a hip fracture was decreased with a hazard ratio (HR) of 0.98 per one point of increase in the Stroop Test (adjusted HR = 0.98, 95% confidence interval [CI]: 0.97-1.00) and 0.93 per one point increase in COWAT (adjusted HR = 0.93, 95% CI: 0.88-0.99).The risk of hip fracture in AD patients was associated with baseline frontal lobe function. The result of this research presents evidence of association between frontal lobe function and risk of hip fracture in patients with AD.

Individual classification of Alzheimer's disease with diffusion magnetic resonance imaging.

PubMed

Schouten, Tijn M; Koini, Marisa; Vos, Frank de; Seiler, Stephan; Rooij, Mark de; Lechner, Anita; Schmidt, Reinhold; Heuvel, Martijn van den; Grond, Jeroen van der; Rombouts, Serge A R B

2017-05-15

Diffusion magnetic resonance imaging (MRI) is a powerful non-invasive method to study white matter integrity, and is sensitive to detect differences in Alzheimer's disease (AD) patients. Diffusion MRI may be able to contribute towards reliable diagnosis of AD. We used diffusion MRI to classify AD patients (N=77), and controls (N=173). We use different methods to extract information from the diffusion MRI data. First, we use the voxel-wise diffusion tensor measures that have been skeletonised using tract based spatial statistics. Second, we clustered the voxel-wise diffusion measures with independent component analysis (ICA), and extracted the mixing weights. Third, we determined structural connectivity between Harvard Oxford atlas regions with probabilistic tractography, as well as graph measures based on these structural connectivity graphs. Classification performance for voxel-wise measures ranged between an AUC of 0.888, and 0.902. The ICA-clustered measures ranged between an AUC of 0.893, and 0.920. The AUC for the structural connectivity graph was 0.900, while graph measures based upon this graph ranged between an AUC of 0.531, and 0.840. All measures combined with a sparse group lasso resulted in an AUC of 0.896. Overall, fractional anisotropy clustered into ICA components was the best performing measure. These findings may be useful for future incorporation of diffusion MRI into protocols for AD classification, or as a starting point for early detection of AD using diffusion MRI. Copyright © 2017 Elsevier Inc. All rights reserved.

Structure-based feeding strategies: A key component of child nutrition.

PubMed

Taylor, Maija B; Emley, Elizabeth; Pratt, Mercedes; Musher-Eizenman, Dara R

2017-07-01

This study examined the relationship between structure, autonomy promotion, and control feeding strategies and parent-reported child diet. Participants (N = 497) were parents of children ages 2.5 to 7.5 recruited from Amazon Mechanical Turk. This sample was a Caucasian (79%), educated sample (61% college graduates) with most reports from mothers (76%). Online survey including measures of parent feeding strategies and child dietary intake. Use of structure-based feeding strategies explained 21% of the variance in child consumption of added sugar, 12% of the variance in child intake of added sugar from sugar-sweetened beverages, and 16% of the variance in child consumption of fruits and vegetables. Higher unhealthy food availability and permissive feeding uniquely predicted higher child added sugar intake and child consumption of added sugar from sugar-sweetened beverages. Greater healthy food availability uniquely predicted higher child fruit and vegetable intake. and Future Directions: In Caucasian educated families, structure-based feeding strategies appear to be a relatively stronger correlate of parent-reported child intake of added sugar and fruits and vegetables as compared to autonomy promotion and control feeding strategies. Longitudinal research may be needed in order to reveal the relationships between autonomy promotion and control feeding strategies with child diet. If future studies have similar findings to this study's results, researchers may want to focus more heavily on investigating the impact of teaching parents stimulus-control techniques and feeding-related assertiveness skills on child dietary intake. Copyright © 2017 Elsevier Ltd. All rights reserved.

Frontal Lobe Function and Risk of Hip Fracture in Patient With Alzheimer Disease

PubMed Central

Roh, Hyun Woong; Hong, Chang Hyung; Lee, SooJin; Lee, Yunhwan; Lee, Kang Soo; Chang, Ki Jung; Oh, Byoung Hoon; Choi, Seong Hye; Kim, Seong Yoon; Back, Joung Hwan; Chung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Son, Sang Joon

2015-01-01

Abstract To determine the association between frontal lobe function and risk of hip fracture in patients with Alzheimer disease (AD). Retrospective cohort study using multicenter hospital-based dementia registry and national health insurance claim data was done. Participants who had available data of neuropsychological test, national health insurance claim, and other covariates were included. A total of 1660 patients with AD were included based on Stroop Test results. A total of 1563 patients with AD were included based on the Controlled Oral Word Association Test (COWAT) results. Hip fracture was measured by validated identification criteria using national health insurance claim data. Frontal lobe function was measured by Stroop Test and COWAT at baseline. After adjusting for potential covariates, including cognitive function in other domains (language, verbal and nonverbal memory, and attention), the Cox proportional hazard regression analysis revealed that risk of a hip fracture was decreased with a hazard ratio (HR) of 0.98 per one point of increase in the Stroop Test (adjusted HR = 0.98, 95% confidence interval [CI]: 0.97–1.00) and 0.93 per one point increase in COWAT (adjusted HR = 0.93, 95% CI: 0.88–0.99). The risk of hip fracture in AD patients was associated with baseline frontal lobe function. The result of this research presents evidence of association between frontal lobe function and risk of hip fracture in patients with AD. PMID:26559259

Reactor performance and energy analysis of solid state anaerobic co-digestion of dairy manure with corn stover and tomato residues.

PubMed

Li, Yangyang; Xu, Fuqing; Li, Yu; Lu, Jiaxin; Li, Shuyan; Shah, Ajay; Zhang, Xuehua; Zhang, Hongyu; Gong, Xiaoyan; Li, Guoxue

2018-03-01

Anaerobic co-digestion is commonly believed to be benefical for biogas production. However, additional of co-substrates may require additional energy inputs and thus affect the overall energy efficiency of the system. In this study, reactor performance and energy analysis of solid state anaerobic digestion (SS-AD) of tomato residues with dairy manure and corn stover were investigated. Different fractions of tomato residues (0, 20, 40, 60, 80 and 100%, based on volatile solid weight (VS)) were co-digested with dairy manure and corn stover at 15% total solids. Energy analysis based on experimental data was conducted for three scenarios: SS-AD of 100% dairy manure, SS-AD of binary mixture (60% dairy manure and 40% corn stover, VS based), and SS-AD of ternary mixture (36% dairy manure, 24% corn stover, and 40% tomato residues, VS based). For each scenario, the energy requirements for individual process components, including feedstock collection and transportation, feedstock pretreatment, biogas plant operation, digestate processing and handling, and the energy production were examined. Results showed that the addition of 20 and 40% tomato residues increased methane yield compared to that of the dairy manure and corn stover mixture, indicating that the co-digestion could balance nutrients and improve the performance of solid-state anaerobic digestion. The energy required for heating substrates had the dominant effect on the total energy consumption. The highest volatile solids (VS) reduction (57.0%), methane yield (379.1 L/kg VS feed ), and net energy production were achieved with the mixture of 24% corn stover, 36% dairy manure, and 40% tomato residues. Thus, the extra energy input for adding tomato residues for co-digestion could be compensated by the increase of methane yield. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rey's Auditory Verbal Learning Test scores can be predicted from whole brain MRI in Alzheimer's disease.

PubMed

Moradi, Elaheh; Hallikainen, Ilona; Hänninen, Tuomo; Tohka, Jussi

2017-01-01

Rey's Auditory Verbal Learning Test (RAVLT) is a powerful neuropsychological tool for testing episodic memory, which is widely used for the cognitive assessment in dementia and pre-dementia conditions. Several studies have shown that an impairment in RAVLT scores reflect well the underlying pathology caused by Alzheimer's disease (AD), thus making RAVLT an effective early marker to detect AD in persons with memory complaints. We investigated the association between RAVLT scores (RAVLT Immediate and RAVLT Percent Forgetting) and the structural brain atrophy caused by AD. The aim was to comprehensively study to what extent the RAVLT scores are predictable based on structural magnetic resonance imaging (MRI) data using machine learning approaches as well as to find the most important brain regions for the estimation of RAVLT scores. For this, we built a predictive model to estimate RAVLT scores from gray matter density via elastic net penalized linear regression model. The proposed approach provided highly significant cross-validated correlation between the estimated and observed RAVLT Immediate (R = 0.50) and RAVLT Percent Forgetting (R = 0.43) in a dataset consisting of 806 AD, mild cognitive impairment (MCI) or healthy subjects. In addition, the selected machine learning method provided more accurate estimates of RAVLT scores than the relevance vector regression used earlier for the estimation of RAVLT based on MRI data. The top predictors were medial temporal lobe structures and amygdala for the estimation of RAVLT Immediate and angular gyrus, hippocampus and amygdala for the estimation of RAVLT Percent Forgetting. Further, the conversion of MCI subjects to AD in 3-years could be predicted based on either observed or estimated RAVLT scores with an accuracy comparable to MRI-based biomarkers.

Development of polymerase chain reaction-based diagnostic tests for detection of Malsoor virus & adenovirus isolated from Rousettus species of bats in Maharashtra, India.

PubMed

Shete, Anita M; Yadav, Pragya; Kumar, Vimal; Nikam, Tushar; Mehershahi, Kurosh; Kokate, Prasad; Patil, Deepak; Mourya, Devendra T

2017-01-01

Bats are recognized as important reservoirs for emerging infectious disease and some unknown viral diseases. Two novel viruses, Malsoor virus (family Bunyaviridae, genus, Phlebovirus) and a novel adenovirus (AdV) (family, Adenoviridae genus, Mastadenovirus), were identified from Rousettus bats in the Maharashtra State of India. This study was done to develop and optimize real time reverse transcription - polymerase chain reaction (RT-PCR) assays for Malsoor virus and real time and nested PCR for adenovirus from Rousettus bats. For rapid and accurate screening of Malsoor virus and adenovirus a nested polymerase chain reaction and TaqMan-based real-time PCR were developed. Highly conserved region of nucleoprotein gene of phleboviruses and polymerase gene sequence from the Indian bat AdV isolate polyprotein gene were selected respectively for diagnostic assay development of Malsoor virus and AdV. Sensitivity and specificity of assays were calculated and optimized assays were used to screen bat samples. Molecular diagnostic assays were developed for screening of Malsoor virus and AdV and those were found to be specific. Based on the experiments performed with different parameters, nested PCR was found to be more sensitive than real-time PCR; however, for rapid screening, real-time PCR can be used and further nested PCR can be used for final confirmation or in those laboratories where real-time facility/expertise is not existing. This study reports the development and optimization of nested RT-PCR and a TaqMan-based real-time PCR for Malsoor virus and AdV. The diagnostic assays can be used for rapid detection of these novel viruses to understand their prevalence among bat population.

Associations between Verbal Learning Slope and Neuroimaging Markers across the Cognitive Aging Spectrum.

PubMed

Gifford, Katherine A; Phillips, Jeffrey S; Samuels, Lauren R; Lane, Elizabeth M; Bell, Susan P; Liu, Dandan; Hohman, Timothy J; Romano, Raymond R; Fritzsche, Laura R; Lu, Zengqi; Jefferson, Angela L

2015-07-01

A symptom of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is a flat learning profile. Learning slope calculation methods vary, and the optimal method for capturing neuroanatomical changes associated with MCI and early AD pathology is unclear. This study cross-sectionally compared four different learning slope measures from the Rey Auditory Verbal Learning Test (simple slope, regression-based slope, two-slope method, peak slope) to structural neuroimaging markers of early AD neurodegeneration (hippocampal volume, cortical thickness in parahippocampal gyrus, precuneus, and lateral prefrontal cortex) across the cognitive aging spectrum [normal control (NC); (n=198; age=76±5), MCI (n=370; age=75±7), and AD (n=171; age=76±7)] in ADNI. Within diagnostic group, general linear models related slope methods individually to neuroimaging variables, adjusting for age, sex, education, and APOE4 status. Among MCI, better learning performance on simple slope, regression-based slope, and late slope (Trial 2-5) from the two-slope method related to larger parahippocampal thickness (all p-values<.01) and hippocampal volume (p<.01). Better regression-based slope (p<.01) and late slope (p<.01) were related to larger ventrolateral prefrontal cortex in MCI. No significant associations emerged between any slope and neuroimaging variables for NC (p-values ≥.05) or AD (p-values ≥.02). Better learning performances related to larger medial temporal lobe (i.e., hippocampal volume, parahippocampal gyrus thickness) and ventrolateral prefrontal cortex in MCI only. Regression-based and late slope were most highly correlated with neuroimaging markers and explained more variance above and beyond other common memory indices, such as total learning. Simple slope may offer an acceptable alternative given its ease of calculation.

Technology-enabled academic detailing: computer-mediated education between pharmacists and physicians for evidence-based prescribing.

PubMed

Ho, Kendall; Nguyen, Anne; Jarvis-Selinger, Sandra; Novak Lauscher, Helen; Cressman, Céline; Zibrik, Lindsay

2013-09-01

Academic detailing (AD) is the practice of specially trained pharmacists with detailed medication knowledge meeting with physicians to share best practices of prescribing. AD has demonstrated efficacy in positively influencing physicians' prescribing behavior. Nevertheless, a key challenge has been that physicians in rural and remote locations, or physicians who are time challenged, have limited ability to participate in face-to-face meetings with academic detailers, as these specially trained academic detailers are primarily urban-based and limited in numbers. To determine the feasibility of using information technologies to facilitate communication between academic detailers and physicians (known as Technology-Enabled Academic Detailing or TEAD) through a comparison to traditional face-to-face academic detailing (AD). Specifically, TEAD is compared to AD in terms of the ability to aid physicians in acquiring evidence-informed prescribing information on diabetes-related medications, measured in terms of time efficiency, satisfaction of both physicians and pharmacists, and quality of knowledge exchange. General Practitioner Physicians (n=105) and pharmacists (n=12) were recruited from across British Columbia. Pharmacists were trained to be academic detailers on diabetes medication usage. Physicians were assigned to one of four intervention groups to receive four academic detailing sessions from trained pharmacists. Intervention groups included: (1) AD only, (2) TEAD only, (3) TEAD crossed over to AD at midpoint, and (4) AD crossed over to TEAD at midpoint. Evaluation included physician-completed surveys before and after each session, pharmacist logs after each detailing session, interviews and focus groups with physicians and pharmacists at study completion, as well as a technical support log to record all phone calls and emails from physicians and pharmacists regarding any technical challenges during the TEAD sessions, or usage of the web portal. Because recruitment was very low for the cross over groups, we analyzed the results in two groups instead: AD only and TEAD only. 354 sessions were conducted (AD=161, TEAD=193). Of these, complete data were available for 300 sessions, which were included in analysis (AD=133, TEAD=167). On average, TEAD sessions were 49min long, and AD sessions 81min long. Overall, physicians enjoyed both modalities of academic detailing (AD and TEAD) because they received information that both reinforced their existing diabetes knowledge and also provided new prescribing insights and approaches. The results suggest that TEAD is an acceptable alternative to AD for providing physicians advice about prescribing. TEAD is more time efficient, facilitates effective knowledge exchange and interprofessional collaboration, and can reach those physicians virtually where face-to-face AD is not possible or practical. Due to logistics, physicians were allocated, rather than randomized, to receive AD and/or TEAD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effects of fat and/or methionine hydroxy analog added to a molasses-urea-based supplement on ruminal and postruminal digestion and duodenal flow of nutrients in beef steers consuming low-quality lovegrass hay

USDA-ARS?s Scientific Manuscript database

Five crossbred beef steers (initial BW = 338.6 ± 7.8 kg) fitted with ruminal and duodenal cannulas were used in a 5 × 5 Latin square design experiment to evaluate the effects of methionine hydroxy analog (MHA) and/or yellow grease (fat) added to a molassesurea-based supplement on intake and characte...

The National Geographic Names Data Base: Phase II instructions

USGS Publications Warehouse

Orth, Donald J.; Payne, Roger L.

1987-01-01

not recorded on topographic maps be added. The systematic collection of names from other sources, including maps, charts, and texts, is termed Phase II. In addition, specific types of features not compiled during Phase I are encoded and added to the data base. Other names of importance to researchers and users, such as historical and variant names, are also included. The rules and procedures for Phase II research, compilation, and encoding are contained in this publication.

Feasibility Report for Hydropower, St. Anthony Falls Locks and Dams, Mississippi River, Minneapolis, Minnesota.

DTIC Science & Technology

1984-02-01

Added Generators and Breakers 116 * ix I~ Table of Contents (cont.) Item Pace Excitation System 117 Connection to Load 117 Bridge Crane 117 Lower St...118 Added Generator and Breaker 119 Excitation System 120 Connection to Load 120 Mobile Crane 120 Civil Features - Upper Falls 120 Powerhouse 121...intermediate plants fully integrated with the base loaded thermal plants in the area. Gavins Point is generally base- loaded to provide steady flows for

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hunsberger, Randolph; Tomberlin, Gregg; Gaul, Chris

As part of the Army Net-Zero Energy Installation program, the Fort Carson Army Base requested that NREL evaluate the feasibility of adding a biomass boiler to the district heating system served by Building 1860. We have also developed an Excel-spreadsheet-based decision support tool--specific to the historic loads served by Building 1860--with which users can perform what-if analysis on gas costs, biomass costs, and other parameters. For economic reasons, we do not recommend adding a biomass system at this time.

Transgene Expression and Host Cell Responses to Replication-Defective, Single-Cycle, and Replication-Competent Adenovirus Vectors.

PubMed

Crosby, Catherine M; Barry, Michael A

2017-02-18

Most adenovirus (Ad) vectors are E1 gene deleted replication defective (RD-Ad) vectors that deliver one transgene to the cell and all expression is based on that one gene. In contrast, E1-intact replication-competent Ad (RC-Ad) vectors replicate their DNA and their transgenes up to 10,000-fold, amplifying transgene expression markedly higher than RD-Ad vectors. While RC-Ad are more potent, they run the real risk of causing adenovirus infections in vector recipients and those that administer them. To gain the benefits of transgene amplification, but avoid the risk of Ad infections, we developed "single cycle" Ad (SC-Ad) vectors. SC-Ads amplify transgene expression and generated markedly stronger and more persistent immune responses than RD-Ad as expected. However, they also unexpectedly generated stronger immune responses than RC-Ad vectors. To explore the basis of this potency here, we compared gene expression and the cellular responses to infection to these vectors in vitro and in vivo. In vitro, in primary human lung epithelial cells, SC- and RC-Ad amplified their genomes more than 400-fold relative to RD-Ad with higher replication by SC-Ad. This replication translated into higher green fluorescent protein (GFP) expression for 48 h by SC- and RC-Ad than by RD-Ad. In vitro, in the absence of an immune system, RD-Ad expression became higher by 72 h coincident with cell death mediated by SC- and RC-Ad and release of transgene product from the dying cells. When the vectors were compared in human THP-1 Lucia- interferon-stimulated gene (ISG) cells, which are a human monocyte cell line that have been modified to quantify ISG activity, RC-Ad6 provoked significantly stronger ISG responses than RD- or SC-Ad. In mice, intravenous or intranasal injection produced up to 100-fold genome replication. Under these in vivo conditions in the presence of the immune system, luciferase expression by RC and SC-Ad was markedly higher than that by RD-Ad. In immunodeficient mice, SC-Ad drove stronger luciferase expression than RC- or RD-Ad. These data demonstrate better transgene expression by SC- and RC-Ad in vitro and in vivo than RD-Ad. This higher expression by the replicating vectors results in a peak of expression within 1 to 2 days followed by cell death of infected cells and release of transgene products. While SC- and RC-Ad expression were similar in mice and in Syrian hamsters, RC-Ad provoked much stronger ISG induction which may explain in part SC-Ad's ability to generate stronger and more persistent immune responses than RC-Ad in Ad permissive hamsters.

The Principal Axis Approach to Value-Added Calculation

ERIC Educational Resources Information Center

He, Qingping; Tymms, Peter

2014-01-01

The assessment of the achievement of students and the quality of schools has drawn increasing attention from educational researchers, policy makers, and practitioners. Various test-based accountability and feedback systems involving the use of value-added techniques have been developed for evaluating the effectiveness of individual teaching…

Intragroup Stigma Among Men Who Have Sex with Men: Data Extraction from Craigslist Ads in 11 Cities in the United States

PubMed Central

Vansia, Dhrutika; Stephenson, Rob

2016-01-01

Background Gay, bisexual, and other men who have sex with men (MSM) regularly experience homophobic discrimination and stigma. While previous research has examined homophobic and HIV-related intergroup stigma originating from non-MSM directed at MSM, less is known about intragroup stigma originating from within MSM communities. While some research has examined intragroup stigma, this research has focused mostly on HIV-related stigma. Intragroup stigma may have a unique influence on sexual risk-taking behaviors as it occurs between sexual partners. Online sexual networking venues provide a unique opportunity to examine this type of stigma. Objective The purpose of this study is to examine the presence and patterns of various types of intragroup stigma represented in Men Seeking Men Craigslist sex ads. Methods Data were collected from ads on Craigslist sites from 11 of the 12 US metropolitan statistical areas with the highest HIV/AIDS prevalence. Two categories of data were collected: self-reported characteristics of the authors and reported biases in the ads. Chi-square tests were used to examine patterns of biases across cities and author characteristics. Results Biases were rarely reported in the ads. The most commonly reported biases were against men who were not “disease and drug free (DDF),” representing stigma against men living with HIV or a sexually transmitted infection. Patterns in bias reporting occurred across cities and author characteristics. There were no variations based on race, but ageism (mostly against older men) varied based on the ad author’s age and self-reported DDF status; bias against feminine gender expression varied based on self-reported sexual orientation; bias against “fat” men varied by self-reported DDF status; bias against “ugly” men varied by a self-report of being good-looking; and bias against people who do not have a DDF status varied based on self-reported HIV status and self-reported DDF status. Conclusions Despite an overall low reporting of biases in ads, these findings suggest that there is a need to address intragroup stigma within MSM communities. The representation of biases and intragroup stigma on Craigslist may result from internalized stigma among MSM while also perpetuating further internalization of stigma for men who read the sex ads. Understanding patterns in the perpetuation of intragroup stigma can help to better target messages aimed at making cultural and behavioral shifts in the perpetration of intragroup stigma within MSM communities. PMID:27227158

Intragroup Stigma Among Men Who Have Sex with Men: Data Extraction from Craigslist Ads in 11 Cities in the United States.

PubMed

Goldenberg, Tamar; Vansia, Dhrutika; Stephenson, Rob

2016-01-01

Gay, bisexual, and other men who have sex with men (MSM) regularly experience homophobic discrimination and stigma. While previous research has examined homophobic and HIV-related intergroup stigma originating from non-MSM directed at MSM, less is known about intragroup stigma originating from within MSM communities. While some research has examined intragroup stigma, this research has focused mostly on HIV-related stigma. Intragroup stigma may have a unique influence on sexual risk-taking behaviors as it occurs between sexual partners. Online sexual networking venues provide a unique opportunity to examine this type of stigma. The purpose of this study is to examine the presence and patterns of various types of intragroup stigma represented in Men Seeking Men Craigslist sex ads. Data were collected from ads on Craigslist sites from 11 of the 12 US metropolitan statistical areas with the highest HIV/AIDS prevalence. Two categories of data were collected: self-reported characteristics of the authors and reported biases in the ads. Chi-square tests were used to examine patterns of biases across cities and author characteristics. Biases were rarely reported in the ads. The most commonly reported biases were against men who were not "disease and drug free (DDF)," representing stigma against men living with HIV or a sexually transmitted infection. Patterns in bias reporting occurred across cities and author characteristics. There were no variations based on race, but ageism (mostly against older men) varied based on the ad author's age and self-reported DDF status; bias against feminine gender expression varied based on self-reported sexual orientation; bias against "fat" men varied by self-reported DDF status; bias against "ugly" men varied by a self-report of being good-looking; and bias against people who do not have a DDF status varied based on self-reported HIV status and self-reported DDF status. Despite an overall low reporting of biases in ads, these findings suggest that there is a need to address intragroup stigma within MSM communities. The representation of biases and intragroup stigma on Craigslist may result from internalized stigma among MSM while also perpetuating further internalization of stigma for men who read the sex ads. Understanding patterns in the perpetuation of intragroup stigma can help to better target messages aimed at making cultural and behavioral shifts in the perpetration of intragroup stigma within MSM communities.

Application of a MRI based index to longitudinal atrophy change in Alzheimer disease, mild cognitive impairment and healthy older individuals in the AddNeuroMed cohort

PubMed Central

Aguilar, Carlos; Muehlboeck, J-Sebastian; Mecocci, Patrizia; Vellas, Bruno; Tsolaki, Magda; Kloszewska, Iwona; Soininen, Hilkka; Lovestone, Simon; Wahlund, Lars-Olof; Simmons, Andrew; Westman, Eric

2014-01-01

Cross sectional studies of patients at risk of developing Alzheimer disease (AD) have identified several brain regions known to be prone to degeneration suitable as biomarkers, including hippocampal, ventricular, and whole brain volume. The aim of this study was to longitudinally evaluate an index based on morphometric measures derived from MRI data that could be used for classification of AD and healthy control subjects, as well as prediction of conversion from mild cognitive impairment (MCI) to AD. Patients originated from the AddNeuroMed project at baseline (119 AD, 119 MCI, 110 controls (CTL)) and 1-year follow-up (62 AD, 73 MCI, 79 CTL). Data consisted of 3D T1-weighted MR images, demographics, MMSE, ADAS-Cog, CERAD and CDR scores, and APOE e4 status. We computed an index using a multivariate classification model (AD vs. CTL), using orthogonal partial least squares to latent structures (OPLS). Sensitivity, specificity and AUC were determined. Performance of the classifier (AD vs. CTL) was high at baseline (10-fold cross-validation, 84% sensitivity, 91% specificity, 0.93 AUC) and at 1-year follow-up (92% sensitivity, 74% specificity, 0.93 AUC). Predictions of conversion from MCI to AD were good at baseline (77% of MCI converters) and at follow-up (91% of MCI converters). MCI carriers of the APOE e4 allele manifested more atrophy and presented a faster cognitive decline when compared to non-carriers. The derived index demonstrated a steady increase in atrophy over time, yielding higher accuracy in prediction at the time of clinical conversion. Neuropsychological tests appeared less sensitive to changes over time. However, taking the average of the two time points yielded better correlation between the index and cognitive scores as opposed to using cross-sectional data only. Thus, multivariate classification seemed to detect patterns of AD changes before conversion from MCI to AD and including longitudinal information is of great importance. PMID:25071554

Discrimination between patients with mild Alzheimer's disease and healthy subjects based on cerebral blood flow images of the lateral views in xenon-enhanced computed tomography.

PubMed

Sase, Shigeru; Yamamoto, Homaro; Kawashima, Ena; Tan, Xin; Sawa, Yutaka

2018-01-01

Quantitative cerebral blood flow (CBF) measurement is expected to help early detection of functional abnormalities caused by Alzheimer's disease (AD) and enable AD treatment to begin in its early stages. Recently, a technique of layer analysis was reported that allowed CBF to be analyzed from the outer to inner layers of the brain. The aim of this work was to develop methods for discriminating between patients with mild AD and healthy subjects based on CBF images of the lateral views created with the layer analysis technique in xenon-enhanced computed tomography. Xenon-enhanced computed tomography using a wide-volume CT was performed on 17 patients with mild AD aged 75 or older and on 15 healthy age-matched volunteers. For each subject, we created CBF images of the right and left lateral views with a depth of 10-15 mm from the surface of the brain. Ten circular regions of interest (ROI) were placed on each image, and CBF was calculated for each ROI. We determined discriminant ROI that had CBF that could be used to differentiate between the AD and volunteer groups. AD patients' CBF range (mean - SD to mean + SD) and healthy volunteers' CBF range (mean - SD to mean + SD) were obtained for each ROI. Receiver-operator curves were created to identify patients with AD for each of the discriminant ROI and for the AD patients' and healthy volunteers' CBF ranges. We selected an ROI on both the right and left temporal lobes as the discriminant ROI. Areas under the receiver-operator curve were 93.3% using the ROI on the right temporal lobe, 95.3% using the ROI on the left temporal lobe, and 92.4% using the AD patients' and healthy volunteers' CBF ranges. We could effectively discriminate between patients with mild AD and healthy subjects using ROI placed on CBF images of the lateral views in xenon-enhanced computed tomography. © 2017 Japanese Psychogeriatric Society.

Adenovirus 4/7 Vaccine's Effect on Disease Rates Is Associated With Disappearance of Adenovirus on Building Surfaces at a Military Recruit Base.

PubMed

Broderick, Michael; Myers, Christopher; Balansay, Melinda; Vo, Scott; Osuna, Angel; Russell, Kevin

2017-11-01

Febrile respiratory illness resulting from adenovirus types 4 and 7 (Ad4/7) was endemic at military training camps, but controlled by an Ad4/7 vaccine from the 1970s to 1999, the year it was discontinued. Thereafter, rates returned to prevaccine levels. Rates dropped after reintroduction of an Ad4/7 vaccine in 2011. Surfaces of the barracks and medical clinic of a training camp were swabbed in 3 studies in 2004 and 1 study in 2007, and tested with culture and polymerase chain reaction (PCR). Similar swabbing was done in 2013 and 2015 and tested with PCR. In the studies before 2011 (prevaccine), 12% of samples were Ad4/7 positive by culture and 27% positive by PCR. In the 2 studies after 2011 (postvaccine), no samples were Ad4/7 positive. The Ad 4/7 vaccine has resulted in the near elimination of Ad4/7-related disease and the disappearance of Ad4/7 from surfaces in a military basic training camp. Renewed transmission of Ad4/7 in this setting would likely require new importation from military recruits and an immunologically naive cohort, which the current vaccination program prevents. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Management of Atopic Dermatitis in Japan.

PubMed

Saeki, Hidehisa

2017-01-01

The guidelines for the treatment of atopic dermatitis (AD) issued by the Japanese Dermatological Association (JDA), which are basically designed for dermatologists, were first prepared in 2000 and revised in 2016. The guidelines for AD of the Japanese Society of Allergology (JSA), which are basically designed for allergologists, including internists, otorhinolaryngologists, ophthalmologists, and dermatologists, were first prepared in 2009 and revised in 2014. In this article, I review the definition, pathophysiology, etiology, epidemiology, diagnosis, severity classification, examination for diagnosis and severity assessment, and treatments for AD in Japan according to these two guidelines for AD (JDA and JSA). Based on the definition and diagnostic criteria for AD of the JDA, patients meeting three basic criteria, 1) pruritus, 2) typical morphology and distribution of the eczema, and 3) chronic or chronically relapsing course, are regarded as having AD. Treatment measures for AD basically consist of drug therapy, skin care, and elimination of exacerbating factors. Drugs that potently reduce AD-related inflammation in the skin are topical corticosteroids and tacrolimus. It is most important to promptly and accurately reduce inflammation related to AD by using these topical anti-inflammatory drugs. Proactive therapy refers to a treatment method in which, after inducing remission, a topical corticosteroid or tacrolimus ointment is intermittently applied to the skin in addition to skin care with moisturizers in order to maintain remission.