Predicting change for individual psychotherapy clients on the basis of their nearest neighbors.

This study extended client-focused research by using the nearest neighbor (NN) approach, a client-specific sampling and prediction strategy derived from research on alpine avalanches. Psychotherapy clients (N = 203) seen in routine practice settings in the United Kingdom completed a battery of intake measures and then completed symptom intensity ratings before each session. Forecasts of each client's rate of change and session-by-session variability were computed on the basis of that client's NNs (n = 10-50 in different comparisons). Alternative forecasts used linear or log-linear slopes and were compared with an alternative prediction strategy. Results showed that the NN approach was superior to the alternative model in predicting rate of change, though the advantage was less clear for predicting variability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Post-pass partitioning of signal processing programs

Symmetric multiprocessor systems are increasingly common, not only as high-throughput servers, but as a vehicle for executing a single application in parallel in order to reduce its execution latency. This article presents Pedigree, a compilation tool that employs a new partitioning heuristic based on the program dependence graph (PDG). Pedigree creates overlapping, potentially interdependent threads, each executing on a subset of the SMP processors that matches the thread’s available parallelism. A unified framework is used to build threads from procedures, loop nests, loop iterations, and smaller constructs. Pedigree does not require any parallel language support; it is post-compilation tool that reads in object code. The SDIO Signal and Data Processing Benchmark Suite has been selected as an example of real-time, latency-sensitive code. Its coarse-grained data flow parallelism is naturally exploited by Pedigree to achieve speedups of 1.63×/2.13× (mean/max) and 1.71×/2.41× on two and four processors, respectively. There is roughly a 20% improvement over existing techniques that exploit only data parallelism. By exploiting the unidirectional flow of data for coarse-grained pipelining, the synchronization overhead is typically limited to less than 6% for synchronization latency of 100 cycles, and less than 2% for 10 cycles. This research was supported by ONR contract numbers N00014-91-J-1518 and N00014-96-1-0347. We would like to thank the Pittsburgh Supercomputing Center for use of their Alpha systems.     

Towards quality requirements via animated formal specifications

Assuring a high quality requirements specification document involves both an early validation process and an increased level of participation. An approach and its supporting environment which combines the benefits of a formal system specification and its subsequent execution via a rapid prototype is reported. The environment assists in the construction, clarification, validation and visualisation of a formal specification. An illustrative case study demonstrates the consequences of assertions about system properties at this early stage of software development. Our approach involves the pragmatic combination of technical benefits of formal systems engineering based techniques with the context‐sensitive notions of increased participation of both developer and user stakeholders to move us closer towards a quality requirements specification document.     

Dissipation of Turbulent Kinetic Energy near a Bubble Plume

Profiles of the rate of dissipation of turbulent kinetic energy were inferred from temperature microstructure measurements near a bubble plume at the center of a tank with diameter of 13.7 m and maximum depth of 8.3 m. Six sets of between 18 and 51 profiles were collected at airflow rates of 0.1–0.6 L/s, measured at atmospheric pressure, and ensemble-averaged dissipation profiles were calculated. The dissipation in all cases was between 10?8 and 10?6?m2/s3 in most of the profile, but it increased sharply near the water surface. Energy considerations are used to discuss the experimental results in terms of previous numerical models of bubble plume turbulence. Two previous numerical studies show that the turbulence dissipates between 15 and 30% of the available power. In the experiments, the fraction is less than 1% because some of the energy of the plume is used to generate waves on the water surface and the profiles used to compute the volume-averaged dissipation were relatively far from the bubble plume.     

The Small Molecule GAL-201 Efficiently Detoxifies Soluble Amyloid β Oligomers: New Approach towards Oral Disease-Modifying Treatment of Alzheimer’s Disease

Soluble amyloid β (Aβ) oligomers have been shown to be highly toxic to neurons and are considered to be a major cause of the neurodegeneration underlying Alzheimer’s disease (AD). That makes soluble Aβ oligomers a promising drug target. In addition to eliminating these toxic species from the patients’ brain with antibody-based drugs, a new class of drugs is emerging, namely Aβ aggregation inhibitors or modulators, which aim to stop the formation of toxic Aβ oligomers at the source. Here, pharmacological data of the novel Aβ aggregation modulator GAL-201 are presented. This small molecule (288.34 g/mol) exhibits high binding affinity to misfolded Aβ_1-42 monomers (K_D = 2.5 ± 0.6 nM). Pharmacokinetic studies in rats using brain microdialysis are supportive of its oral bioavailability. The Aβ oligomer detoxifying potential of GAL-201 has been demonstrated by means of single cell recordings in isolated hippocampal neurons (perforated patch experiments) as well as in vitro and in vivo extracellular monitoring of long-term potentiation (LTP, in rat transverse hippocampal slices), a cellular correlate for synaptic plasticity. Upon preincubation, GAL-201 efficiently prevented the detrimental effect on LTP mediated by Aβ_1-42 oligomers. Furthermore, the potential to completely reverse an already established neurotoxic process could also be demonstrated. Of particular note in this context is the self-propagating detoxification potential of GAL-201, leading to a neutralization of Aβ oligomer toxicity even if GAL-201 has been stepwise removed from the medium (serial dilution), likely due to prion-like conformational changes in Aβ_1-42 monomer aggregates (trigger effect). The authors conclude that the data presented strongly support the further development of GAL-201 as a novel, orally available AD treatment with potentially superior clinical profile.     

Proteomic Biomarkers of the Apnea Hypopnea Index and Obstructive Sleep Apnea: Insights into the Pathophysiology of Presence,Severity, and Treatment Response

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea–hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke.     

Warning: statistical benchmarking is addictive. Kicking the habit in machine learning

Algorithm performance evaluation is so entrenched in the machine learning community that one could call it an addiction. Like most addictions, it is harmful and very difficult to give up. It is harmful because it has serious limitations. Yet, we have great faith in practicing it in a ritualistic manner: we follow a fixed set of rules telling us the measure, the data sets and the statistical test to use. When we read a paper, even as reviewers, we are not sufficiently critical of results that follow these rules. Here, we will debate what are the limitations and how to best address them. This article may not cure the addiction but hopefully it will be a good first step along that road.     

Eliminating Synaptic Ribbons from Rods and Cones Halves the Releasable Vesicle Pool and Slows Down Replenishment

Glutamate release from rod and cone photoreceptor cells involves presynaptic ribbons composed largely of the protein RIBEYE. To examine roles of ribbons in rods and cones, we studied mice in which GCamP3 replaced the B-domain of RIBEYE. We discovered that ribbons were absent from rods and cones of both knock-in mice possessing GCamP3 and conditional RIBEYE knockout mice. The mice lacking ribbons showed reduced temporal resolution and contrast sensitivity assessed with optomotor reflexes. ERG recordings showed 50% reduction in scotopic and photopic b-waves. The readily releasable pool (RRP) of vesicles in rods and cones measured using glutamate transporter anion currents (I_A(glu)) was also halved. We also studied the release from cones by stimulating them optogenetically with ChannelRhodopsin2 (ChR2) while recording postsynaptic currents in horizontal cells. Recovery of the release from paired pulse depression was twofold slower in the rods and cones lacking ribbons. The release from rods at −40 mV in darkness involves regularly spaced multivesicular fusion events. While the regular pattern of release remained in the rods lacking ribbons, the number of vesicles comprising each multivesicular event was halved. Our results support conclusions that synaptic ribbons in rods and cones expand the RRP, speed up vesicle replenishment, and augment some forms of multivesicular release. Slower replenishment and a smaller RRP in photoreceptors lacking ribbons may contribute to diminished temporal frequency responses and weaker contrast sensitivity.