Ultrasound-targeted microbubble destruction enhances AAV mediated gene transfection: human RPE cells in vitro and the rat retina in vivo

The present study was performed to investigate the efficacy and safety of Ultrasound-targeted microbubble destruction (UTMD) mediated rAAV2-EGFP to cultured human retinal pigment epithelium (RPE) cells _in vitro_ and the rat retina _in vivo_. _In vitro_ study, cultured human RPE cells were exposed to US under different conditions with or without microbubbles. Furthermore, the effect of UTMD to rAAV2-EGFP itself and the cells were evaluated. _In vivo_ study, gene transfer was examined by injecting rAAV2-EGFP into the subretinal space of the rats with or without microbubbles and then exposed to US. We investigated EGFP expression _in vivo_ via stereomicroscopy and performed quantitative analysis by Axiovision 3.1 software. HE staining and frozen sections were used to observe tissue damage and location of EGFP gene expression. _In vitro_ study, the transfection efficiency of rAAV2-EGFP increased 74.85% under the optimal UTMD conditions. Furthermore, there was almost no cytotoxicity to the cells and rAAV2-EGFP itself. _In vivo_ study, UTMD could be used safely to enhance and accelerate transgene expression of the retina. Fluorescence expression was mainly located in the layer of retina. UTMD is a promising method for gene delivery to the retina

Decision-making after continuous wins or losses in a randomized guessing task: implications for how the prior selection results affect subsequent decision-making

BACKGROUND: Human decision-making is often affected by prior selections and their outcomes, even in situations where decisions are independent and outcomes are unpredictable. METHODS: In this study, we created a task that simulated real-life non-strategic gambling to examine the effect of prior outcomes on subsequent decisions in a group of male college students. RESULTS: Behavioral performance showed that participants needed more time to react after continuous losses (LOSS) than continuous wins (WIN) and discontinuous outcomes (CONTROL). In addition, participants were more likely to repeat their selections in both WIN and LOSS conditions. Functional MRI data revealed that decisions in WINs were associated with increased activation in the mesolimbic pathway, but decreased activation in the inferior frontal gyrus relative to LOSS. Increased prefrontal cortical activation was observed during LOSS relative to WIN and CONTROL conditions. CONCLUSION: Taken together, the behavioral and neuroimaging findings suggest that participants tended to repeat previous selections during LOSS trials, a pattern resembling the gambler’s fallacy. However, during WIN trials, participants tended to follow their previous lucky decisions, like the ‘hot hand’ fallacy

Assessing Cost-Effectiveness of the Conservation Reserve Program and its Interaction with Crop Insurance Subsidies

Strong demand for agricultural commodities, high crop prices and pressure to reduce government budget deficits heighten the need for land retirement programs to be designed to maximize environmental benefits for any given budget outlay. The Conservation Reserve Program (CRP) is the largest land retirement program while the federal crop insurance program (FCIP) is the largest federal program supporting U.S. agriculture. We examine the environmental and budgetary implications of alternative CRP enrollment mechanisms in the context of the program’s interactions with FCIP. We demonstrate that the current CRP enrollment mechanism is inconsistent with cost-effective targeting. We also identify a cost-effective targeting enrollment mechanism that maximizes total environmental benefits under a budget constraint. Since federal crop insurance subsidies will not be incurred when a tract of land is retired from agricultural production, we consider the impacts when avoided subsidies are accounted for in designing a land-retirement program. Based on contract-level CRP offer data in 2003 and 2011 across the contiguous United States, we find that adopting the cost-effective targeting enrollment mechanism can increase CRP acreage by up to 45% and total environmental benefits by up to 21% while leaving government outlay unchanged. Incorporating crop insurance subsidies into the land retirement design can increase avoided subsidies caused by CRP enrollment and environmental benefits obtained from CRP. The government can enroll significant acres at zero real cost. Under cost-effective targeting, CRP acreage and payments would increase in the Great Plains and the Southeastern states but would decrease in the Midwest

Distribution and prevalence of malaria parasites among long-tailed macaques (Macaca fascicularis) in regional populations across Southeast Asia.

BackgroundPlasmodium knowlesi and Plasmodium cynomolgi are two malaria parasites naturally transmissible between humans and wild macaque through mosquito vectors, while Plasmodium inui can be experimentally transmitted from macaques to humans. One of their major natural hosts, the long-tailed macaque (Macaca fascicularis), is host to two other species of Plasmodium (Plasmodium fieldi and Plasmodium coatneyi) and is widely distributed in Southeast Asia. This study aims to determine the distribution of wild macaques infected with malarial parasites by examining samples derived from seven populations in five countries across Southeast Asia.MethodsPlasmodium knowlesi, P. cynomolgi, P. coatneyi, P. inui and P. fieldi, were detected using nested PCR assays in DNA samples from 276 wild-caught long-tailed macaques. These samples had been derived from macaques captured at seven locations, two each in the Philippines (n = 68) and Indonesia (n = 70), and one each in Cambodia (n = 54), Singapore (n = 40) and Laos (n = 44). The results were compared with previous studies of malaria parasites in long-tailed macaques from other locations in Southeast Asia. Fisher exact test and Chi square test were used to examine the geographic bias of the distribution of Plasmodium species in the macaque populations.ResultsOut of 276 samples tested, 177 were Plasmodium-positive, with P. cynomolgi being the most common and widely distributed among all long-tailed macaque populations (53.3 %) and occurring in all populations examined, followed by P. coatneyi (20.4 %), P. inui (12.3 %), P. fieldi (3.4 %) and P. knowlesi (0.4 %). One P. knowlesi infection was detected in a macaque from Laos, representing the first documented case of P. knowlesi in wildlife in Laos. Chi square test showed three of the five parasites (P. knowlesi, P. coatneyi, P. cynomolgi) with significant bias in prevalence towards macaques from Malaysian Borneo, Cambodia, and Southern Sumatra, respectively.ConclusionsThe prevalence of malaria parasites, including those that are transmissible to humans, varied among all sampled regional populations of long-tailed macaques in Southeast Asia. The new discovery of P. knowlesi infection in Laos, and the high prevalence of P. cynomolgi infections in wild macaques in general, indicate the strong need of public advocacy in related countries