'The risks of playing it safe': a prospective longitudinal study of response to reward in the adolescent offspring of depressed parents

BACKGROUND Alterations in reward processing may represent an early vulnerability factor for the development of depressive disorder. Depression in adults is associated with reward hyposensitivity and diminished reward seeking may also be a feature of depression in children and adolescents. We examined the role of reward responding in predicting depressive symptoms, functional impairment and new-onset depressive disorder over time in the adolescent offspring of depressed parents. In addition, we examined group differences in reward responding between currently depressed adolescents, psychiatric and healthy controls, and also cross-sectional associations between reward responding and measures of positive social/environmental functioning. Method We conducted a 1-year longitudinal study of adolescents at familial risk for depression (n = 197; age range 10-18 years). Reward responding and self-reported social/environmental functioning were assessed at baseline. Clinical interviews determined diagnostic status at baseline and at follow-up. Reports of depressive symptoms and functional impairment were also obtained. RESULTS Low reward seeking predicted depressive symptoms and new-onset depressive disorder at the 1-year follow-up in individuals free from depressive disorder at baseline, independently of baseline depressive symptoms. Reduced reward seeking also predicted functional impairment. Adolescents with current depressive disorder were less reward seeking (i.e. bet less at favourable odds) than adolescents free from psychopathology and those with externalizing disorders. Reward seeking showed positive associations with social and environmental functioning (extra-curricular activities, humour, friendships) and was negatively associated with anhedonia. There were no group differences in impulsivity, decision making or psychomotor slowing. CONCLUSIONS Reward seeking predicts depression severity and onset in adolescents at elevated risk of depression. Adaptive reward responses may be amenable to change through modification of existing preventive psychological interventions

Endoscopic Submucosal Tunnel Dissection as a Novel Therapeutic Technique in Patients With Barrett’s Esophagus

© 2020 American Federation for Medical Research. With the ameliorated resectability prowess of endoscopic techniques, a myriad of diseases previously treated by major ablative surgeries are now endoscopically curable. Endoscopic submucosal tunnel dissection (ESTD) is a relatively new technique that has diversified endoscopic application. Although ESTD has frequently been used for the resection of esophageal neoplastic lesions, the clinical evidence pertaining to its efficacy in the treatment of circumferential Barrett’s esophagus remains sparse. In this study, we evaluated ESTD as a potential therapeutic technique in patients with Barrett’s esophagus-related high-grade dysplasia. The tunneling strategy helped achieve complete en bloc resection at an increased dissection speed, without any procedural complications. This article illustrates that ESTD can be a feasible, safe, and effective treatment for dysplastic Barrett’s esophagus. Future research should aim to stratify the potential risks and complications associated with this optimization of endoscopic submucosal dissection in patients with superficial esophageal lesions

Numerical versus analytical accuracy of the formulas for light propagation

Numerical integration of the differential equations of light propagation in the Schwarzschild metric shows that in some situations relevant for practical observations the well-known post-Newtonian solution for light propagation has an error up to 16 microarcsecond. The aim of this work is to demonstrate this fact, identify the reason for this error and to derive an analytical formula accurate at the level of 1 microarcsecond as needed for high-accuracy astrometric projects (e.g., Gaia). An analytical post-post-Newtonian solution for the light propagation for both Cauchy and boundary problems is given for the Schwarzschild metric augmented by the PPN and post-linear parameters $\beta$, $\gamma$ and $\epsilon$. Using analytical upper estimates of each term we investigate which post-post-Newtonian terms may play a role for an observer in the solar system at the level of 1 microarcsecond and conclude that only one post-post-Newtonian term remains important for this numerical accuracy. In this way, an analytical solution for the boundary problem for light propagation is derived. That solution contains terms of both post-Newtonian and post-post-Newtonian order, but is valid for the given numerical level of 1 microarcsecond. The derived analytical solution has been verified using the results of a high-accuracy numerical integration of differential equations of light propagation and found to be correct at the level well below 1 microarcsecond for arbitrary observer situated within the solar system. Furthermore, the origin of the post-post-Newtonian terms relevant for the microarcsecond accuracy is elucidated. We demonstrate that these terms result from an inadequate choice of the impact parameter in the standard post-Newtonian formulas

Barkhausen Noise in a Relaxor Ferroelectric

Barkhausen noise, including both periodic and aperiodic components, is found in and near the relaxor regime of a familiar relaxor ferroelectric, PbMg$_{1/3}$Nb$_{2/3}$O$_3$, driven by a periodic electric field. The temperature dependences of both the amplitude and spectral form show that the size of the coherent dipole moment changes shrink as the relaxor regime is entered, contrary to expectations based on some simple models.Comment: 4 pages RevTeX4, 5 figures; submitted to Phys Rev Let

A Titan exploration study: Science, technology, and mission planning options, volume 2

For abstract, see Vol.

Asteroids in the Inner Solar System II - Observable Properties

This paper presents synthetic observations of long-lived, coorbiting asteroids of Mercury, Venus, the Earth and Mars. Our sample is constructed by taking the limiting semimajor axes, differential longitudes and inclinations for long-lived stability provided by simulations. The intervals are randomly populated with values to create initial conditions. These orbits are re-simulated to check that they are stable and then re-sampled every 2.5 years for 1 million years. The Mercurian sample contains only horseshoe orbits, the Martian sample only tadpoles. For both Venus and the Earth, the greatest concentration of objects on the sky occurs close to the classical Lagrange points at heliocentric ecliptic longitudes of 60 and 300 degrees. The distributions are broad especially if horseshoes are present in the sample. The full-width half maximum (FWHM) in heliocentric longitude for Venus is 325 degrees and for the Earth is 328 degrees. The mean and most common velocity of these coorbiting satellites coincides with the mean motion of the parent planet, but again the spread is wide with a FWHM for Venus of 27.8 arcsec/hr and for the Earth of 21.0 arcsec/hr. For Mars, the greatest concentration on the sky occurs at heliocentric ecliptic latitudes of 12 degrees. The peak of the velocity distribution occurs at 65 arcsec/hr, significantly less than the Martian mean motion, while its FWHM is 32.3 arcsec/hr. The case of Mercury is the hardest of all, as the greatest concentration occurs at heliocentric longitudes close to the Sun.Comment: 16 pages, 11 figures, Monthly Notices (in press). Higher quality figures available at http://www-thphys.physics.ox.ac.uk/users/WynEvans/home.htm

A Titan exploration study: Science, technology and mission planning options, volume 1

Mission concepts and technology advancements that can be used in the exploration of the outer planet satellites were examined. Titan, the seventh satellite of Saturn was selected as the target of interest. Science objectives for Titan exploration were identified, and recommended science payloads for four basic mission modes were developed (orbiter, atmospheric probe, surface penetrator and lander). Trial spacecraft and mission designs were produced for the various mission modes. Using these trial designs as a base, technology excursions were then made to find solutions to the problems resulting from these conventional approaches and to uncover new science, technology and mission planning options. Several mission modes were developed that take advantage of the unique conditions expected at Titan. They include a combined orbiter, atmosphere probe and lander vehicle, a combined probe and surface penetrator configuration and concepts for advanced remote sensing orbiters

Inference of single-cell phylogenies from lineage tracing data using Cassiopeia.

The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia-a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Together, these should broadly enable large-scale mammalian lineage tracing efforts. Cassiopeia and its benchmarking resources are publicly available at www.github.com/YosefLab/Cassiopeia

Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats.

Vampire bats (Desmodus rotundus) are obligate blood feeders that have evolved specialized systems to suit their sanguinary lifestyle. Chief among such adaptations is the ability to detect infrared radiation as a means of locating hotspots on warm-blooded prey. Among vertebrates, only vampire bats, boas, pythons and pit vipers are capable of detecting infrared radiation. In each case, infrared signals are detected by trigeminal nerve fibres that innervate specialized pit organs on the animal's face. Thus, vampire bats and snakes have taken thermosensation to the extreme by developing specialized systems for detecting infrared radiation. As such, these creatures provide a window into the molecular and genetic mechanisms underlying evolutionary tuning of thermoreceptors in a species-specific or cell-type-specific manner. Previously, we have shown that snakes co-opt a non-heat-sensitive channel, vertebrate TRPA1 (transient receptor potential cation channel A1), to produce an infrared detector. Here we show that vampire bats tune a channel that is already heat-sensitive, TRPV1, by lowering its thermal activation threshold to about 30 °C. This is achieved through alternative splicing of TRPV1 transcripts to produce a channel with a truncated carboxy-terminal cytoplasmic domain. These splicing events occur exclusively in trigeminal ganglia, and not in dorsal root ganglia, thereby maintaining a role for TRPV1 as a detector of noxious heat in somatic afferents. This reflects a unique organization of the bat Trpv1 gene that we show to be characteristic of Laurasiatheria mammals (cows, dogs and moles), supporting a close phylogenetic relationship with bats. These findings reveal a novel molecular mechanism for physiological tuning of thermosensory nerve fibres