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Revised diagnostic criteria for Alzheimer disease (AD) acknowledge a key role of imaging biomarkers for early diagnosis. Diagnostic accuracy depends on whichmarker (i.e., amyloid imaging, 18F-fluorodeoxyglucose FDG-PET, SPECT, MRI) as well as howit is measured (“metric”: visual, manual, semiautomated, or automated segmentationcomputation). We evaluated diagnostic accuracy of marker vs metric in separating AD from healthy and prognostic accuracy to predict progression in mild cognitive impairment. The outcome measure was positive (negative) likelihood ratio, LR (LR−), defined as the ratio between the probability of positive (negative) test outcome in patients and the probability of positive (negative) test outcome in healthy controls. Diagnostic LR of markers was between 4.4 and 9.4 and LR− between 0.25 and 0.08, whereas prognostic LR and LR− were between 1.7 and 7.5, and 0.50 and 0.11, respectively. Within metrics, LRs varied up to 100-fold: LR from approximately 1 to 100; LR− from approximately 1.00 to 0.01. Markers accounted for 11 and 18 of diagnostic and prognostic variance of LR and 16 and 24 of LR−. Across all markers, metrics accounted for an equal or larger amount of variance than markers: 13 and 62 of diagnostic and prognostic variance of LR, and 29 and 18 of LR−. Within markers, the largest proportion of diagnostic LR and LR− variability was within 18F-FDG-PET and MRI metrics, respectively. Diagnostic and prognostic accuracy of imaging AD biomarkers is at least as dependent on how the biomarker is measured as on the biomarker itself. Standard operating procedures are key to biomarker use in the clinical routine and drug trials.

SUMMARY Many clinical trials for Alzheimer’s disease and related disorders struggle to achieve enrollment goals, hampering the progress of research. To help address this problem, the Alzheimer’s Association® has developed and implemented a new clinical trial-matching service designed to increase awareness of ongoing clinical trials among potential participants, improve initial matching of potential participants to enrollment criteria and thus help investigators achieve enrollment goals. This service, Alzheimer’s Association TrialMatch™, uses numerous personal and disease characteristics to match users with potential clinical trials that are currently enrolling participants. It provides users with direct access to trained professional consultants who interpret and explain an individual’s eligibility for specific clinical trials and is designed for use by patients, caregivers, healthy volunteers, physicians and other healthcare providers and researchers. During the first year of operation (July 2010–June 2011), the service received almost 45,000 queries and more than 11,000 completed profiles, which led to 2784 referrals to clinical trials. At least 163 participants of the service are known to have enrolled in a clinical trial. Participants self-report their enrollment into trials.

As multicore architectures enter the mainstream, there is a pressing demand for high-level programming models that can effectively map to them. Stream programming offers an attractive way to expose coarse-grained parallelism, as streaming applications (image, video, DSP, etc.) are naturally represented by independent filters that communicate over explicit data channels.In this paper, we demonstrate an end-to-end stream compiler that attains robust multicore performance in the face of varying application characteristics. As benchmarks exhibit different amounts of task, data, and pipeline parallelism, we exploit all types of parallelism in a unified manner in order to achieve this generality. Our compiler, which maps from the StreamIt language to the 16-core Raw architecture, attains a 11.2x mean speedup over a single-core baseline, and a 1.84x speedup over our previous work.

Although microfluidic chips have demonstrated basic functionality for single applications, performing varied and complex experiments on a single device is still technically challenging. While many groups have implemented control software to drive the pumps, valves, and electrodes used to manipulate fluids in microfluidic devices, a new level of programmability is needed for end users to orchestrate their own unique experiments on a given device. This paper presents an approach for programmable and scalable control of discrete fluid samples in a polydimethylsiloxane (PDMS) microfluidic system using multiphase flows. An immiscible fluid phase is utilized to separate aqueous samples from one another, and a novel “microfluidic latch” is used to precisely align a sample after it has been transported a long distance through the flow channels. To demonstrate the scalability of the approach, this paper introduces a “general-purpose” microfluidic chip containing a rotary mixer and addressable storage cells. The system is general purpose in that all operations on the chip operate in terms of unit-sized aqueous samples; using the underlying mechanisms for sample transport and storage, additional sensors and actuators can be integrated in a scalable manner. A novel high-level software library allows users to specify experiments in terms of variables (i.e., fluids) and operations (i.e., mixes) without the need for detailed knowledge about the underlying device architecture. This research represents a first step to provide a programmable interface to the microfluidic realm, with the aim of enabling a new level of scalability and flexibility for lab-on-a-chip experiments.

Myosin light chains were isolated from cat gastroc-nemius and soleus muscles rendered paraplegic for 1 year and from the vastus lateralis of six patients with Duchenne muscular dystrophy. Despite the altered pattern of function of these muscles, no alterations were noted in the type or relative proportion of these myosin light chains when compared to control muscles.

Experiments with cats showed that imipramine hydrochloride (Tofranil) resembled trimethadione (Tridione) and ethosuximide (Zarontin) in its ability to depress the corticofugal inhibition of afferent activity in the spinal trigeminal nucleus. Imipramine was, therefore, given to a group of 20 patients with petit mal and minor motor seizures who had failed to respond to conventional anticonvulsant medications or had become refractory to them. Fifteen patients had a good initial response to 1 to 3 mg/kg of imipramine hydrochloride, and six of them have continued to show a significant therapeutic response for more than one year. Imipramine thus appears to have the anticonvulsant effect predicted by our experimental data. Our observations suggest that the ability to depress cortical inhibitory pathways is an important feature of drugs that prevent minor seizures.