Using practice effects for targeted trials or sub-group analysis in Alzheimer\u27s disease: How practice effects predict change over time

OBJECTIVE: To describe the presence of practice effects in persons with Alzheimer disease (AD) or mild cognitive impairment (MCI) and to evaluate how practice effects affect cognitive progression and the outcome of clinical trials. METHODS: Using data from a meta-database consisting of 18 studies including participants from the Alzheimer disease Cooperative Study (ADCS) and the Alzheimer Disease Neuroimaging Initiative (ADNI) with ADAS-Cog11 as the primary outcome, we defined practice effects based on the improvement in the first two ADAS-Cog11 scores and then estimated the presence of practice effects and compared the cognitive progression between participants with and without practice effects. The robustness of practice effects was investigated using CDR SB, an outcome independent the definition itself. Furthermore, we evaluated how practice effects can affect sample size estimation. RESULTS: The overall percent of practice effects for AD participants was 39.0% and 53.3% for MCI participants. For AD studies, the mean change from baseline to 2 years was 12.8 points for the non-practice effects group vs 7.4 for the practice effects group; whereas for MCI studies, it was 4.1 for non-practice effects group vs 0.2 for the practice effects group. AD participants without practice effects progressed 0.9 points faster than those with practice effects over a period of 2 years in CDR-SB; whereas for MCI participants, the difference is 0.7 points. The sample sizes can be different by over 35% when estimated based on participants with/without practice effects. CONCLUSION: Practice effects were prevalent and robust in persons with AD or MCI and affected the cognitive progression and sample size estimation. Planning of future AD or MCI clinical trials should account for practice effects to avoid underpower or considers target trials or stratification analysis based on practice effects

Cultural Aspects on Child's Development and Parenting in Manggarai, East Nusa Tenggara, Indonesia

This paper describes the influence of culture in defining the concept of a child, the stages of development and parenting of children in Manggarai, Flores, East Nusa Tenggara. The main questions are how do Manggaraian people define a child in their culture? How do people divide the stages of child development? What do parenting styles develop by the people to their children? How are these concepts different and similar to the general psychological concept about children? This paper was based on a qualitative research. The methods used were ethnography and grounded theory. Through these two mix approaches, the study is to explore and analyze the culture of Manggarai. The research found that: 1) the concept of a child in Manggarai depends on the way the people understand family and community rather than understand a child as just an individual. 2) There are three main stages of childhood development within the culture of Manggarai; 3) As a patriarchal community, the Manggarai people have unique parenting style to the son and daughter; 4). One unique parenting style within the culture of Manggarai was to educate a child to “fear of spirits and ancestors”

The Development of an Evaluational Process for the Group Home Project of the Northeast Multnomah District of Childrens\u27 Service Division

Childrens\u27 Services Division of the State of Oregon is involved in a group home project. They have to date nine group homes in operation within Multnomah County. Their staff consists of a director, three social workers and the group home provider staff. The primary goal for this practicum was the development of an evaluative system that would establish descriptions of the type of client who entered the Group Home Program and some criteria for success in that program. In developing this system, it was necessary to design instruments to measure behavioral changes and attitudes and also to collect descriptive data. Such a system should be as comprehensive as possible while remaining fairly simple and easy to implement. A secondary goal was to pre-test the evaluative system and gather data for the use of the Group Home Project. The instruments could be used continuously in an on-going evaluative process with pre-test data as a standard by which to set more definite objectives and evaluation of the program. Finally the information gathered could be valuable for the 1975 Legislative review

A narnavirus-like element from the trypanosomatid protozoan parasite Leptomonas seymouri

Genome sequences were determined for a novel RNA virus, Leptomonas seymouri Narna-like virus 1 (LepseyNLV1). A 2.9-kb segment encodes an RNA-dependent RNA polymerase (RdRp), while a smaller 1.5-kb segment showed no database search matches. This is the first report of bisegmented Narnaviridae from insect trypanosomatids

Optimizing agents with genetic programming : an evaluation of hyper-heuristics in dynamic real-time logistics

Dynamic pickup and delivery problems (PDPs) require online algorithms for managing a fleet of vehicles. Generally, vehicles can be managed either centrally or decentrally. A common way to coordinate agents decentrally is to use the contract-net protocol (CNET) that uses auctions to allocate tasks among agents. To participate in an auction, agents require a method that estimates the value of a task. Typically this method is an optimization algorithm. Recently, hyper-heuristics has been proposed for automated design of heuristics. Two properties of automatically designed heuristics are particularly promising: 1) a generated heuristic computes quickly, it is expected therefore that hyper-heuristics heuristics perform especially well for urgent problems, and 2) by using simulationbased evaluation, hyper-heuristics can learn from the past and can therefore create a ‘rule of thumb’ that anticipates situations in the future. In the present paper we empirically evaluate whether hyper-heuristics, more specifically genetic programming (GP), can be used to improve agents decentrally coordinated via CNET. We compare several GP settings and compare the resulting heuristic with existing centralized and decentralized algorithms on a dynamic PDP dataset with varying levels of dynamism, urgency, and scale. The results indicate that the evolved heuristic always outperforms the optimization algorithm in the decentralized MAS and often outperforms the centralized optimization algorithm. Our paper shows that designing MASs using genetic programming is an effective way to obtain competitive performance compared to traditional operational research approaches. These results strengthen the relevance of decentralized agent based approaches in dynamic logistics

A novel bunyavirus-like virus of trypanosomatid protist parasites

We report here the sequences for all three segments of a novel RNA virus (LepmorLBV1) from the insect trypanosomatid parasite Leptomonas moramango. This virus belongs to a newly discovered group of bunyavirus-like elements termed Leishbunyaviruses (LBV), the first discovered from protists related to arboviruses infecting humans

A Narnavirus in the trypanosomatid protist plant pathogen Phytomonas serpens

We describe here a new RNA virus (PserNV1) from the plant protist parasite Phytomonas serpens (family Trypanosomatidae, Kinetoplastida, supergroup Excavata). The properties of PserNV1 permit assignment to the genus Narnavirus (Narnaviridae), the first reported from a host other than fungi or oomycetes

Retrieving Nuclear Information from Protons Propagating through A Thick Target

The multiple scattering of high-energy particles in a thick target is fromulated in an impact parameter representation. A formalism similar but not identical to that of Moliere is obtained. We show that calculations of particle beam broadening due to multiple Coulomb scattering alone can be given in closed form. The focus of this study is on whether or not the broadening of the Coulomb angular distribution prevents the retrieval of nuclear-interaction information from mesauring the angular distributions of charged partiles scattered from a thick target. For this purpose, we study multiple scatterings with both the nuclear and Coulomb interactions included and we do not make a small-angle expansion. Condition for retrieving nuclear infomration from high-energy protons propagating through a block of material are obtained.Comment: 29 pages, 13 figure

Role of A20 in cIAP-2 Protection against Tumor Necrosis Factor α (TNF-α)-Mediated Apoptosis in Endothelial Cells

Tumor necrosis factor α (TNF-α) influences endothelial cell viability by altering the regulatory molecules involved in induction or suppression of apoptosis. However, the underlying mechanisms are still not completely understood. In this study, we demonstrated that A20 (also known as TNFAIP3, tumor necrosis factor α-induced protein 3, and an anti-apoptotic protein) regulates the inhibitor of apoptosis protein-2 (cIAP-2) expression upon TNF-α induction in endothelial cells. Inhibition of A20 expression by its siRNA resulted in attenuating expression of TNF-α-induced cIAP-2, yet not cIAP-1 or XIAP. A20-induced cIAP-2 expression can be blocked by the inhibition of phosphatidyl inositol-3 kinase (PI3-K), but not nuclear factor (NF)-κB, while concomitantly increasing the number of endothelial apoptotic cells and caspase 3 activation. Moreover, TNF-α-mediated induction of apoptosis was enhanced by A20 inhibition, which could be rescued by cIAP-2. Taken together, these results identify A20 as a cytoprotective factor involved in cIAP-2 inhibitory pathway of TNF-α-induced apoptosis. This is consistent with the idea that endothelial cell viability is dependent on interactions between inducers and suppressors of apoptosis, susceptible to modulation by TNF-α