2,710 research outputs found
Practical quality control tools for curves and surfaces
Curves (geometry) and surfaces created by Computer Aided Geometric Design systems in the engineering environment must satisfy two basic quality criteria: the geometric shape must have the desired engineering properties; and the objects must be parameterized in a way which does not cause computational difficulty for geometric processing and engineering analysis. Interactive techniques are described which are in use at Boeing to evaluate the quality of aircraft geometry prior to Computational Fluid Dynamic analysis, including newly developed methods for examining surface parameterization and its effects
Estimation of causal effects using instrumental variables with nonignorable missing covariates: Application to effect of type of delivery NICU on premature infants
Understanding how effective high-level NICUs (neonatal intensive care units
that have the capacity for sustained mechanical assisted ventilation and high
volume) are compared to low-level NICUs is important and valuable for both
individual mothers and for public policy decisions. The goal of this paper is
to estimate the effect on mortality of premature babies being delivered in a
high-level NICU vs. a low-level NICU through an observational study where there
are unmeasured confounders as well as nonignorable missing covariates. We
consider the use of excess travel time as an instrumental variable (IV) to
control for unmeasured confounders. In order for an IV to be valid, we must
condition on confounders of the IV---outcome relationship, for example, month
prenatal care started must be conditioned on for excess travel time to be a
valid IV. However, sometimes month prenatal care started is missing, and the
missingness may be nonignorable because it is related to the not fully measured
mother's/infant's risk of complications. We develop a method to estimate the
causal effect of a treatment using an IV when there are nonignorable missing
covariates as in our data, where we allow the missingness to depend on the
fully observed outcome as well as the partially observed compliance class,
which is a proxy for the unmeasured risk of complications. A simulation study
shows that under our nonignorable missingness assumption, the commonly used
estimation methods, complete-case analysis and multiple imputation by chained
equations assuming missingness at random, provide biased estimates, while our
method provides approximately unbiased estimates. We apply our method to the
NICU study and find evidence that high-level NICUs significantly reduce deaths
for babies of small gestational age, whereas for almost mature babies like 37
weeks, the level of NICUs makes little difference. A sensitivity analysis is
conducted to assess the sensitivity of our conclusions to key assumptions about
the missing covariates. The method we develop in this paper may be useful for
many observational studies facing similar issues of unmeasured confounders and
nonignorable missing data as ours.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS699 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Stronger instruments via integer programming in an observational study of late preterm birth outcomes
In an optimal nonbipartite match, a single population is divided into matched
pairs to minimize a total distance within matched pairs. Nonbipartite matching
has been used to strengthen instrumental variables in observational studies of
treatment effects, essentially by forming pairs that are similar in terms of
covariates but very different in the strength of encouragement to accept the
treatment. Optimal nonbipartite matching is typically done using network
optimization techniques that can be quick, running in polynomial time, but
these techniques limit the tools available for matching. Instead, we use
integer programming techniques, thereby obtaining a wealth of new tools not
previously available for nonbipartite matching, including fine and near-fine
balance for several nominal variables, forced near balance on means and optimal
subsetting. We illustrate the methods in our on-going study of outcomes of
late-preterm births in California, that is, births of 34 to 36 weeks of
gestation. Would lengthening the time in the hospital for such births reduce
the frequency of rapid readmissions? A straightforward comparison of babies who
stay for a shorter or longer time would be severely biased, because the
principal reason for a long stay is some serious health problem. We need an
instrument, something inconsequential and haphazard that encourages a shorter
or a longer stay in the hospital. It turns out that babies born at certain
times of day tend to stay overnight once with a shorter length of stay, whereas
babies born at other times of day tend to stay overnight twice with a longer
length of stay, and there is nothing particularly special about a baby who is
born at 11:00 pm.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS582 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer's Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein.
Developing effective therapeutics for complex diseases such as late-onset, sporadic Alzheimer's disease (SAD) is difficult due to genetic and environmental heterogeneity in the human population and the limitations of existing animal models. Here, we used hiPSC-derived neurons to test a compound that stabilizes the retromer, a highly conserved multiprotein assembly that plays a pivotal role in trafficking molecules through the endosomal network. Using this human-specific system, we have confirmed previous data generated in murine models and show that retromer stabilization has a potentially beneficial effect on amyloid beta generation from human stem cell-derived neurons. We further demonstrate that manipulation of retromer complex levels within neurons affects pathogenic TAU phosphorylation in an amyloid-independent manner. Taken together, our work demonstrates that retromer stabilization is a promising candidate for therapeutic development in AD and highlights the advantages of testing novel compounds in a human-specific, neuronal system
Hippocampal Subregions Differentially Associate with Standardized Memory Tests
Recent studies suggest that individual hippocampal subregions perform distinct cognitive operations and are differentially targeted by aging and disease. Although originally developed to assess global hippocampal function, whether performance on standard memory tests used in neuropsychological batteries is associated with individual hippocampal subregions remains unknown. Here we addressed this issue by imaging 210 neuropsychologically characterized subjects using a high-resolution variant of functional magnetic resonance imaging that generates maps reflective of basal hippocampal metabolism. Regression analysis revealed memory tests that differentially associate with two hippocampal subregions, the entorhinal cortex (EC) and the dentate gyrus (DG). Whereas performance on the delayed retention component of the Selective Reminding Test was associated with the EC, performance on the recognition component of the Benton Visual Retention Test (BVRT) was associated with the DG. Furthermore, elevation in blood glucose, previously shown to target the DG, was found to correlate selectively with the recognition component of the BVRT. These findings provide further evidence that the hippocampal subregions perform distinct roles, and, interpreted in the context of previous neuropsychological and imaging studies, confirm that aging and Alzheimer's disease target different hippocampal subregions
Erectile response to intracavernous injection of vasoactive drugs after penile prosthesis removal
Two patients with a history of penile prosthesis removal presented for non-prosthetic treatment of their erectile dysfunction. The first patient had a penile implant for two years before it was removed and showed extensive cavernosal fibrosis. He did not respond to intracavernosal injection of vasoactive drugs. The second patient had the prosthesis for four weeks. He showed no evidence of cavernosal fibrosis and responded well to the intracavernous injection. He has been in an iniracavernous autoinjection program for more than one year without complications
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