Theory Summary and Future Directions

Summary talk at the Lepton-Photon Symposium, Cornell University, Aug. 10-15, 1993.Comment: (Talk presented at the Lepton-Photon Symposium, Cornell University, Aug. 10-15, 1993.) 19 page

An X-ray visualization facility for large-scale multiphase flows

Multiphase flows exist in several industries throughout the world. In 1998 in the United States alone, the economic value of multiphase flows was estimated to b

Processing prescriptively incorrect comparative particles: Evidence from sentence-matching and eye-tracking

Speakers of a language sometimes use particular constructions which violate prescriptive grammar rules. Despite their prescriptive ungrammaticality, they can occur rather frequently. One such example is the comparative construction in Dutch and similarly in German, where the equative particle is used in comparative constructions instead of the prescriptively correct comparative particle (Dutch beter als Jan and German besser wie Jan ‘lit. better as John’). From a theoretical linguist’s point of view, these so-called grammatical norm violations are perfectly grammatical, even though they are not part of the language’s prescriptive grammar. In a series of three experiments using sentence-matching and eye-tracking methodology, we investigated whether grammatical norm violations are processed as truly grammatical, as truly ungrammatical, or whether they fall in between these two. We hypothesized that the latter would be the case. We analyzed our data using linear mixed effects models in order to capture possible individual differences. The results of the sentence-matching experiments, which were conducted in both Dutch and German, showed that the grammatical norm violation patterns with ungrammatical sentences in both languages. Our hypothesis was therefore not borne out. However, using the more sensitive eye-tracking method on Dutch speakers only, we found that the ungrammatical alternative leads to higher reading times than the grammatical norm violation. We also found significant individual variation regarding this very effect. We furthermore replicated the processing difference between the grammatical norm violation and the prescriptively correct variant. In summary, we conclude that while the results of the more sensitive eye-tracking experiment suggest that grammatical norm violations are not processed on a par with ungrammatical sentences, the results of all three experiments clearly show that grammatical norm violations cannot be considered grammatical, either

Terahertz quantum cascade laser as local oscillator in a heterodyne receiver

Terahertz quantum cascade lasers have been investigated with respect to their performance as a local oscillator in a heterodyne receiver. The beam profile has been measured and transformed in to a close to Gaussian profile resulting in a good matching between the field patterns of the quantum cascade laser and the antenna of a superconducting hot electron bolometric mixer. Noise temperature measurements with the hot electron bolometer and a 2.5 THz quantum cascade laser yielded the same result as with a gas laser as local oscillator. (C) 2005 Optical Society of America

Expiratory flow rate, breath hold and anatomic dead space influence electronic nose ability to detect lung cancer

BACKGROUND: Electronic noses are composites of nanosensor arrays. Numerous studies showed their potential to detect lung cancer from breath samples by analysing exhaled volatile compound pattern ("breathprint"). Expiratory flow rate, breath hold and inclusion of anatomic dead space may influence the exhaled levels of some volatile compounds; however it has not been fully addressed how these factors affect electronic nose data. Therefore, the aim of the study was to investigate these effects. METHODS: 37 healthy subjects (44 +/- 14 years) and 27 patients with lung cancer (60 +/- 10 years) participated in the study. After deep inhalation through a volatile organic compound filter, subjects exhaled at two different flow rates (50 ml/sec and 75 ml/sec) into Teflon-coated bags. The effect of breath hold was analysed after 10 seconds of deep inhalation. We also studied the effect of anatomic dead space by excluding this fraction and comparing alveolar air to mixed (alveolar + anatomic dead space) air samples. Exhaled air samples were processed with Cyranose 320 electronic nose. RESULTS: Expiratory flow rate, breath hold and the inclusion of anatomic dead space significantly altered "breathprints" in healthy individuals (p 0.05). These factors also influenced the discrimination ability of the electronic nose to detect lung cancer significantly. CONCLUSIONS: We have shown that expiratory flow, breath hold and dead space influence exhaled volatile compound pattern assessed with electronic nose. These findings suggest critical methodological recommendations to standardise sample collections for electronic nose measurements

Mobile Manipulation of a Laser-induced Breakdown Spectrometer for Planetary Exploration

Laser-induced Breakdown Spectroscopy (LIBS) is an established analytical technique to measure the elemental composition of rocks and other matter on the Martian surface. We propose an autonomous in-contact sampling method based on an attachable LIBS instrument, designed to measure the composition of samples on the surface of planets and moons. The spectrometer module is picked up by our Lightweight Rover Unit (LRU) at the landing site and transported to the sampling location, where the manipulator establishes a solid contact between the instrument and the sample. The rover commands the instrument to trigger the measurement, which in turn releases a laser-pulse and captures the spectrum of the resulting plasma. The in-contact deployment ensures a suitable focus distance for the spectrometer, without a focusing system that would add to the instrument’s volume and weight, and allows for flexible deployment of the instrument. The autonomous software computes all necessary manipulation operations on-board the rover and requires almost no supervision from mission control. We tested the LRU and the LIBS instrument at the moon analogue test site on Mt. Etna, Sicily and successfully demonstrated multiple LIBS measurements, in which the rover automatically deployed the instrument on a rock sample, recorded a measurement and sent the data to mission control, with sufficient quality to distinguish the major elements of the recorded sample

IgG4+ B-Cell receptor clones distinguish IgG4-related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies.

IgG4-related disease of the biliary tree and pancreas is difficult to distinguish from sclerosing cholangitis and biliary/pancreatic malignancies. An accurate noninvasive test for diagnosis and monitoring of disease activity is lacking. We demonstrate that dominant IgG4+ B-cell receptor (BCR) clones determined by nextgeneration sequencing (NGS) accurately distinguish patients with IgG4-associated cholangitis/autoimmune pancreatitis (n=34) from those with primary sclerosing cholangitis (n=17) and biliary/pancreatic malignancies (n=17). A novel, more affordable, widely applicable quantitative polymerase chain reaction (qPCR) protocol analyzing the IgG4/IgG RNA-ratio in blood, also achieves excellent diagnostic accuracy (n=125). Moreover, this qPCR-test performed better than serum IgG4 levels in sensitivity (94% versus 86%) and specificity (99% versus 73%), and correlates with treatment response (n=20). Conclusion: IgG4+ BCR clones and IgG4/IgG RNA-ratiomarkedly improve delineation, early diagnosis and monitoring of IgG4-related disease of the biliary tree and pancreas

Artificial intelligence-based classification of motor unit action potentials in real-world needle EMG recordings

ObjectiveTo develop an artificial neural network (ANN) for classification of motor unit action potential (MUAP) duration in real-word, unselected and uncleaned needle electromyography (n-EMG) recordings.MethodsTwo nested ANN models were trained, the first discerning muscle rest, contraction and artifacts in n-EMG recordings from 2674 individual muscles from 326 patients obtained as part of daily care. The second ANN model subsequently used segments labeled as contraction for prediction of prolonged, normal and shortened MUAPs. Model performance was assessed in one internal and two external validation datasets of 184, 30 and 50 muscles, respectively.ResultsThe first model discerned rest, contraction and artifacts with an accuracy of 96%. The second model predicted prolonged, normal and shortened MUAPs with an accuracy of 67%, 83% and 68% in the different validation sets.ConclusionsWe developed a two-step ANN that classifies rest, muscle contraction and artifacts from real-world n-EMG recordings with very high accuracy. MUAP duration classification had moderate accuracy.SignificanceThis is the first study to show that an ANN can classify MUAPs in real-world n-EMG recordings highlighting the potential for AI assisted MUAP classification as a clinical tool.Neurological Motor Disorder

Pitfalls and practical suggestions for using local field potential recordings in DBS clinical practice and research.


Local field potential (LFP) recordings using chronically implanted sensing-enabled stimulators are a powerful tool for indexing symptom presence and severity in neurological and neuropsychiatric disorders, and for enhancing our neurophysiological understanding of brain processes. LFPs have gained interest as input signals for closed-loop deep brain stimulation (DBS) and can be used to inform DBS parameter selection. LFP recordings using chronically implanted sensing-enabled stimulators have various implementational challenges.
Approach: Here we describe our collective experience using BrainSense (Medtronic®) for clinical and research work. We aim to provide insightful tips and practical advice to empower readers with the knowledge needed to navigate the intricacies of the device and make the most out of its features.
Main results:
The central issues that apply to several BrainSense features encompass restricted compatibility of stimulation configuration with sensing, differences in electrophysiological signal properties between 'stimulation OFF' and 'stimulation ON at 0.0 mA', and challenges associated with the internal clock of the neurostimulator. In addition, since recordings are obtained from bipolar and not monopolar channels, spatial certainty regarding the distribution of LFPs around the DBS electrode is limited. Several options exist to synchronize LFP time series with external data streams, but standardization and generalization are lacking. The use of at-home chronic LFP recording is limited by a low temporal and spectral resolution. Regarding at-home LFP snapshots, LFP time series are not stored, parts of the power spectrum are censored when stimulating at high or low frequencies, and the stimulation amplitude is not readily available.
Significance: We discussed practical applications, implementation, system limitations, and pitfalls with the aim that sensing can be better applied for clinical practice and research.&#xD

Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum

Abstract Genome-wide association studies (GWASs) may help inform the etiology of infertility. Here, we perform GWAS meta-analyses across seven cohorts in up to 42,629 cases and 740,619 controls and identify 25 genetic risk loci for male and female infertility. We additionally identify up to 269 genetic loci associated with follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone through sex-specific GWAS meta-analyses (n = 6,095–246,862). Exome sequencing analyses reveal that women carrying testosterone-lowering rare variants in some genes are at risk of infertility. However, we find no local or genome-wide genetic correlation between female infertility and reproductive hormones. While infertility is genetically correlated with endometriosis and polycystic ovary syndrome, we find limited genetic overlap between infertility and obesity. Finally, we show that the evolutionary persistence of infertility-risk alleles may be explained by directional selection. Taken together, we provide a comprehensive view of the genetic determinants of infertility across multiple diagnostic criteria.Abstract Genome-wide association studies (GWASs) may help inform the etiology of infertility. Here, we perform GWAS meta-analyses across seven cohorts in up to 42,629 cases and 740,619 controls and identify 25 genetic risk loci for male and female infertility. We additionally identify up to 269 genetic loci associated with follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone through sex-specific GWAS meta-analyses (n = 6,095–246,862). Exome sequencing analyses reveal that women carrying testosterone-lowering rare variants in some genes are at risk of infertility. However, we find no local or genome-wide genetic correlation between female infertility and reproductive hormones. While infertility is genetically correlated with endometriosis and polycystic ovary syndrome, we find limited genetic overlap between infertility and obesity. Finally, we show that the evolutionary persistence of infertility-risk alleles may be explained by directional selection. Taken together, we provide a comprehensive view of the genetic determinants of infertility across multiple diagnostic criteria