Goal-Focused Emotion-Regulation Therapy (GET) for young adult survivors of testicular cancer: a pilot randomized controlled trial of a biobehavioral intervention protocol.

BackgroundTesticular cancer diagnosis and treatment, especially given its threat to sexuality and reproductive health, can be distressing in the formative period of young adulthood and the majority of young survivors experience impairing, distressing, and modifiable adverse outcomes that can persist long after medical treatment. These include psychological distress, impairment in pursuit of life goals, persistent physical side effects, elevated risk of secondary malignancies and chronic illness, and biobehavioral burden (e.g., enhanced inflammation, dysregulated diurnal stress hormones). However, few targeted interventions exist to assist young survivors in renegotiating life goals and regulating cancer-related emotions, and none focus on reducing the burden of morbidity via biobehavioral mechanisms. This paper describes the methodology of a randomized controlled biobehavioral trial designed to investigate the feasibility and preliminary impact of a novel intervention, Goal-focused Emotion-Regulation Therapy (GET), aimed at improving distress symptoms, emotion regulation, goal navigation skills, and stress-sensitive biomarkers in young adult testicular cancer patients.MethodsParticipants will be randomized to receive six sessions of GET or Individual Supportive Therapy (ISP) delivered over 8 weeks. In addition to indicators of intervention feasibility, we will measure primary (depressive and anxiety symptoms) and secondary (emotion regulation and goal navigation skills, career confusion) psychological outcomes prior to (T0), immediately after (T1), and 12 weeks after (T2) intervention. Additionally, identified biomarkers will be measured at baseline and at T2.DiscussionGET may have the potential to improve self-regulation across biobehavioral domains, improve overall cancer adjustment, and address the need for targeted supportive care interventions for young adult cancer survivors.Trial registrationClinicaltrials.gov, NCT04150848. Registered on 28 October 2019

Utilizing the Alarm Taxonomy and Classification System (ATACS) to Redesign Landing Gear Warnings

Alarms have been in use for many decades, yet there still needs to be more clarity about what makes a good alarm. Vendors and government agencies have developed several useful handbooks describing the Do’s and Don’ts of effective alarm design; however, to date, we cannot find a comprehensive quantitative taxonomy or classification system that allows researchers to easily score and rank various alarm designs in any field—while using a common language that users, engineers, designers, and human factors professionals can understand. The Alarm Taxonomy and Classification System (ATACS) fills this gap in the literature by breaking alarms down into categorical characteristics, providing a quantitative methodology for scoring each characteristic, and outlining a process by which users, vendors, and human factors professionals can agree on the efficacy of the alarm in question. We discuss this process in detail and show how this system was used to improve landing gear warnings

C-terminal motif prediction in eukaryotic proteomes using comparative genomics and statistical over-representation across protein families

<p>Abstract</p> <p>Background</p> <p>The carboxy termini of proteins are a frequent site of activity for a variety of biologically important functions, ranging from post-translational modification to protein targeting. Several short peptide motifs involved in protein sorting roles and dependent upon their proximity to the C-terminus for proper function have already been characterized. As a limited number of such motifs have been identified, the potential exists for genome-wide statistical analysis and comparative genomics to reveal novel peptide signatures functioning in a C-terminal dependent manner. We have applied a novel methodology to the prediction of C-terminal-anchored peptide motifs involving a simple z-statistic and several techniques for improving the signal-to-noise ratio.</p> <p>Results</p> <p>We examined the statistical over-representation of position-specific C-terminal tripeptides in 7 eukaryotic proteomes. Sequence randomization models and simple-sequence masking were applied to the successful reduction of background noise. Similarly, as C-terminal homology among members of large protein families may artificially inflate tripeptide counts in an irrelevant and obfuscating manner, gene-family clustering was performed prior to the analysis in order to assess tripeptide over-representation across protein families as opposed to across all proteins. Finally, comparative genomics was used to identify tripeptides significantly occurring in multiple species. This approach has been able to predict, to our knowledge, all C-terminally anchored targeting motifs present in the literature. These include the PTS1 peroxisomal targeting signal (SKL*), the ER-retention signal (K/HDEL*), the ER-retrieval signal for membrane bound proteins (KKxx*), the prenylation signal (CC*) and the CaaX box prenylation motif. In addition to a high statistical over-representation of these known motifs, a collection of significant tripeptides with a high propensity for biological function exists between species, among kingdoms and across eukaryotes. Motifs of note include a serine-acidic peptide (DSD*) as well as several lysine enriched motifs found in nearly all eukaryotic genomes examined.</p> <p>Conclusion</p> <p>We have successfully generated a high confidence representation of eukaryotic motifs anchored at the C-terminus. A high incidence of true-positives in our results suggests that several previously unidentified tripeptide patterns are strong candidates for representing novel peptide motifs of a widely employed nature in the C-terminal biology of eukaryotes. Our application of comparative genomics, statistical over-representation and the adjustment for protein family homology has generated several hypotheses concerning the C-terminal topology as it pertains to sorting and potential protein interaction signals. This approach to background reduction could be expanded for application to protein motif prediction in the protein interior. A parallel N-terminal analysis is presented as supplementary data.</p

The Efficacy and Optimization of Somatosensory Intracortical Microstimulation in Rats

Demand exists for brain-machine interfaces that offer a wide range of sensory feedback along with volitional motor control to individuals with limited control of natural sensory or motor function. As these sensorimotor devices are developed, it is necessary to improve the interaction between the prostheses and higher-level cortical structures. Optimizing these somatosensory stimulation parameters will require the use of a high-throughput experimental design. To address this, one Sprague-Dawley rat was trained to respond to auditory stimuli during a conditioned-avoidance behavior task and then implanted with a penetrating microelectrode array in the part of the somatosensory cortex corresponding to the left forelimb. After implantation, the task was repeated using electrical stimuli instead of auditory signals. Detection threshold data was collected from each electrode site to prove stimulation efficacy. The pulse rate of electrical stimulation was varied to optimize power usage by the neuroprosthesis while still achieving the lowest possible thresholds. Electrical impedance spectroscopy and cyclic voltammetry data were collected to monitor the performance of the electrode. Testing shows that auditory learning can be translated to somatosensory stimulation. As an aggregate, somatosensory detection thresholds are significantly different from those in the auditory cortex (Student’s t-test, p \u3c 0.0003). With these results in mind, future research can further optimize somatosensory intracortical microstimulation to provide more sensory feedback in motor prostheses

Realization of the Einstein-Podolsky-Rosen Paradox Using Momentum- and Position-Entangled Photons from Spontaneous Parametric Down Conversion

We report on a momentum-position realization of the EPR paradox using direct detection in the near and far fields of the photons emitted by collinear type-II phase-matched parametric down conversion. Using this approach we achieved a measured two-photon momentum-position variance product of 0.01ℏ2, which dramatically violates the bounds for the EPR and separability criteria

Identifying metabolites from protein identifiers with P2M

The identification of metabolites from complex biological samples often involves matching experimental mass spectrometry data to signatures of compounds derived from massive chemical databases. However, misidentifications may result due to the complexity of potential chemical space that leads to databases containing compounds with nearly identical structures. Prior knowledge of compounds that may be enzymatically consumed or produced by an organism can help reduce misidentifications by restricting initial database searching to compounds that are likely to be present in a biological system. While databases such as UniProt allow for the identification of small molecules that may be consumed or generated by enzymes encoded in an organism's genome, currently no tool exists for identifying SMILES strings of metabolites associated with protein identifiers and expanding R-containing substructures to fully defined, biologically relevant chemical structures. Here we present Proteome2Metabolome (P2M), a tool that performs these tasks using external database querying behind a simple command line interface. Beyond mass spectrometry based applications, P2M can be generally used to identify biologically relevant chemical structures likely to be observed in a biological system

Quantum and Classical Coincidence Imaging

Coincidence, or ghost, imaging is a technique that uses two correlated optical fields to form an image of an object. In this work we identify aspects of coincidence imaging which can be performed with classically correlated light sources and aspects which require quantum entanglement. We find that entangled photons allow high-contrast, high-resolution imaging to be performed at any distance from the light source. We demonstrate this fact by forming ghost images in the near and far fields of an entangled photon source, noting that the product of the resolutions of these images is a factor of 3 better than that which is allowed by classical diffraction theory

Extremely Metal-Poor Stars. VII. The Most Metal-Poor Dwarf, CS 22876-032

We report high-resolution, high-signal-to-noise, observations of the extremely metal-poor double-lined spectroscopic binary CS 22876-032. The system has a long period : P = 424.7 $\pm$ 0.6 days. It comprises two main sequence stars having effective temperatures 6300 K and 5600 K, with a ratio of secondary to primary mass of 0.89 $\pm$ 0.04. The metallicity of the system is [Fe/H] = -3.71 $\pm$ 0.11 $\pm$ 0.12 (random and systematic errors) -- somewhat higher than previous estimates. We find [Mg/Fe] = 0.50, typical of values of less extreme halo material. [Si/Fe], [Ca/Fe], and [Ti/Fe], however, all have significantly lower values, ~ 0.0-0.1, suggesting that the heavier elements might have been underproduced relative to Mg in the material from which this object formed. In the context of the hypothesis that the abundance patterns of extremely metal-poor stars are driven by individual enrichment events and the models of Woosley and Weaver (1995), the data for CS 22876-032 are consistent with its having been enriched by a zero-metallicity supernova of mass 30 M$_{\odot}$. As the most metal-poor near-main-sequence-turnoff star currently known, the primary of the system has the potential to strongly constrain the primordial lithium abundance. We find A(Li) (= log(N(Li)/N(H)) + 12.00) = 2.03 $\pm$ 0.07, which is consistent with the finding of Ryan et al. (1999) that for stars of extremely low metallicity A(Li) is a function of [Fe/H].Comment: 27 pages, 9 figures, accepted for publication in The Astrophysical Journal, Sept. 1, 2000 issu