Thomas NW, Paré M. Temporal processing of saccade targets in parietal cortex area LIP during visual search. J Neurophysiol 97: [942][943][944][945][946][947] 2007. First published November 1, 2006; doi:10.1152/jn.00413.2006. We studied whether the lateral intraparietal (LIP) area-a subdivision of parietal cortex anatomically interposed between visual cortical areas and saccade executive centers-contains neurons with activity patterns sufficient to contribute to the active process of selecting saccade targets in visual search. Visually responsive neurons were recorded while monkeys searched for a color-different target presented concurrently with seven distractors evenly distributed in a circular search array. We found that LIP neurons initially responded indiscriminately to the presentation of a visual stimulus in their response fields, regardless of its feature and identity. Their activation nevertheless evolved to signal the search target before saccade initiation: an ideal observer could reliably discriminate the target from the individual activation of 60% of neurons, on average, 138 ms after stimulus presentation and 26 ms before saccade initiation. Importantly, the timing of LIP neuronal discrimination varied proportionally with reaction times. These findings suggest that LIP activity reflects the selection of both the search target and the targeting saccade during active visual search.
Entecavir is an oral antiviral drug with selective activity against hepatitis B virus (HBV). We conducted a randomized, placebo-controlled, dose-escalating study in patients with chronic hepatitis B infection in which we evaluated the efficacy and safety of entecavir given for 28 days. Follow-up was 24 weeks. All doses of entecavir (0.05 mg, 0.1 mg, 0.5 mg, and 1.0 mg) showed a pronounced suppression of replication of the HBV with a 2.21, 2.29, 2.81, and 2.55 mean log 10 reduction of viral load, respectively. Approximately 25% of patients on entecavir showed a decline of HBV DNA below the limit of detection of the Chiron HBV-DNA assay (<0.7 MEq/mL). In the postdosing follow-up period patients who were treated with 0.5 and 1.0 mg of entecavir showed a considerably slower return in their HBV DNA levels to baseline compared with those patients treated with lower dosages (P < .05). All doses of entecavir were well tolerated with no significant difference between treated patients and those receiving placebo. No significant changes in alanine transaminase (ALT) levels within the dose groups and the placebo group between baseline and the end of treatment were observed. Three patients (9%) (1 each in the 0.05-, 0.1-, and 0.5-mg groups) experienced asymptomatic hepatitis flares 16 weeks (2 patients) and 24 weeks (1 patient) after withdrawal of entecavir. In conclusion, in this 28-day study of entecavir a pronounced decrease of HBV DNA was observed and there were no significant side effects in entecavir patients in comparison with placebo-treated patients. (HEPATOLOGY 2001;34:578-582.)Although the introduction of an effective vaccine against hepatitis B has drastically reduced the incidence of new infections, more than three hundred million people are affected by chronic hepatitis B infection worldwide. The infection may eventually lead to a substantial percentage of deaths caused by cirrhosis with complications of liver failure and hepatocellular carcinoma. 1 Interferon alfa has been the only registered therapy during recent years but it is effective in only one third of patients, 2 requires parenteral administration, and causes many side effects especially in cases of cirrhosis. 3 Lamivudine, a cytosine nucleoside analogue, is an orally administered antiviral agent with few side effects. It has recently been registered for the treatment of chronic hepatitis B infection. [4][5][6] However, the development of mutations with decreased sensitivity of the virus for lamivudine, 7-9 and the rebound of viral replication after withdrawal of the drug 10,11 leave room for further improvement of nucleoside analogue therapy. The increase in viral replication after withdrawal of the drug is based on residual covalently closed circular DNA (cccDNA) inside the nucleus of the hepatocyte, which is not affected by lamivudine. 12,13 Entecavir, a new deoxyguanine nucleoside analogue, is a selective inhibitor of the replication of the hepatitis B virus (HBV). 14-16 In HepG2.2.15 cell lines, this compound has proved to be 30 times more potent...
<b><i>Introduction:</i></b> Future digital health research hinges on methodologies to conduct remote clinical assessments and in-home monitoring. The Collaborative Aging Research Using Technology (CART) initiative was introduced to establish a digital technology research platform that could widely assess activity in the homes of diverse cohorts of older adults and detect meaningful change longitudinally. This paper reports on the built end-to-end design of the CART platform, its functionality, and the resulting research capabilities. <b><i>Methods:</i></b> CART platform development followed a principled design process aiming for scalability, use case flexibility, longevity, and data privacy protection while allowing sharability. The platform, comprising ambient technology, wearables, and other sensors, was deployed in participants’ homes to provide continuous, long-term (months to years), and ecologically valid data. Data gathered from CART homes were sent securely to a research server for analysis and future data sharing. <b><i>Results:</i></b> The CART system was created, iteratively tested, and deployed to 232 homes representing four diverse cohorts (African American, Latinx, low-income, and predominantly rural-residing veterans) of older adults (<i>n</i> = 301) across the USA. Multiple measurements of wellness such as cognition (e.g., mean daily computer use time = 160–169 min), physical mobility (e.g., mean daily transitions between rooms = 96–155), sleep (e.g., mean nightly sleep duration = 6.3–7.4 h), and level of social engagement (e.g., reports of overnight visitors = 15–45%) were collected across cohorts. <b><i>Conclusion:</i></b> The CART initiative resulted in a minimally obtrusive digital health-enabled system that met the design principles while allowing for data capture over extended periods and can be widely used by the research community. The ability to monitor and manage health digitally within the homes of older adults is an important alternative to in-person assessments in many research contexts. Further advances will come with wider, shared use of the CART system in additional settings, within different disease contexts, and by diverse research teams.
Aims: We explored the relationship between objective and subjective measures of burden prior to and after a telehealth-based caregiver intervention. One caregiver participated in two studies, one to assess the feasibility of objective, home-based monitoring (EVALUATE-AD), the second to assess the feasibility of a caregiver education telehealth-based intervention, Tele-STAR. Methods: Subjective measures of burden and depression in Tele-STAR and objective measures related to daily activities of the caregiver in EVALUATE-AD were compared to examine trends between the different outcome measures. Results: While the caregiver reported an increase in distressing behaviors by her partner, burden levels did not significantly change during or after the Tele-STAR intervention, while objective measures of activity and sleep showed a slight decline. Conclusion: Unobtrusive home-based monitoring may provide a novel, objective method to assess the effectiveness of caregiver intervention programs.
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