Colorado Sleep Institute

The formation of terrestrial planets from a ring of planetesimals was initially proposed by Hansen (2009) as a solution to the planet’s mass distribution pattern, namely with two small planets at the edges of the semi major axis distribution and two major ones at the center, rather than a system of planets with uniform masses.An early attempt to explain why planetesimals should have been concentrated into a ring invoked a specific inward-then-outward migration pattern of Jupiter, dubbed the Grand Tack (Walsh et al., 2011). However, modern models of planetesimal formation predict that the first planetesimals naturally form in rings (Drazkowska et al., 2016; Morbidelli et al., 2022; Izidoro et al., 2022; Marchall and Morbidelli, 2024). These works support the fundaments of the ring formation model.Whereas early simulations of terrestrial planet formations assumed the existence of a narrow ring of planetesimals and planetary embryos after gas removal (Hansen et al., 2009; Nesvorny et al., 2021), more recent simulations start from a ring of sole planetesimals (super-particles) and simulate the growth of planetary embryos during the gas-disk stage (Woo et al. 2023, 2024). This phase leads to the spreading of the ring and the formation of numerous mini-planets, unless the radial profile of the gas surface density distribution peaks itself near 1 au (Broz et al., 2021). In these conditions, it is not necessary that the ring of planetesimals is located at 1 au.Although the terrestrial planets formed from almost exclusively non-carbonaceous material from the inner Solar system, the chemistry of the Earth’s mantle, in particular the moderately siderophile element depletion pattern and FeO and SiO2 abundances, reveal that our planet should have started its accretion by incorporating reduced material, akin (in terms of oxygen fugacity) to Aubrites and enstatite chondrites, and incorporated later more oxidized material, akin to the known non-carbonaceous iron meteorite parent bodies or of ordinary chondrites (Rubie et al., 2011). This cannot be explained if the terrestrial planets formed from a narrow ring of planetesimals (Dale et al., 2025 and at this conference).New, still unpublished models will be presented in this review, where the terrestrial planets form from two rings. The first ring, located near 0.5 au, is due to the silicate sublimation line and comprises reduced planetesimals, where the second one, located near 1.5 au, is made of more oxidized planetesimals. The growth of planetary embryos from each of these rings, and their merging near 1 au, gives the best reconstruction of the orbital and mass distribution of the terrestrial planets. The existence of the second ring is justified in Goldberg et al., this conference).In conclusions, the model of terrestrial planet formation from a ring of planetesimals is definitely more complicated than originally envisioned by Hansen (2009) but is now converging towards a more complex model that can explain both the physical, chemical and isotopic properties of the planets. Moreover, the new model is consistent with the structure of the asteroid belt and with our understanding of the evolution of the giant planets.Acknowledgment: This work is supported by the ERC grant N. 101019380 HolyEarthReferences.Hansen, B.M.S., 2009. Formation of the Terrestrial Planets from a Narrow Annulus. 703, 1131–1140. doi:10.1088/0004-637X/703/1/1131,Walsh, K.J., Morbidelli, A., Raymond, S.N., O’Brien, D.P., Mandell, A.M., 2011. A low mass for Mars from Jupiter’s early gas-driven migration. 475, 206–209. doi:10.1038/nature10201Drążkowska, J.,Alibert,Y.,Moore, B., 2016. Close-in planetesimal formation by pile-up of drifting pebbles. 594,A105. doi:10.1051/0004-6361/201628983,Morbidelli, A., Baillié, K., Batygin, K., Charnoz, S., Guillot, T., Rubie, D.C., Kleine, T., 2022. Contemporary formation of early Solar System planetesimals at two distinct radial locations. Nature Astronomy 6, 72–79. doi:10.1038/s41550-021-01517-7,Izidoro, A., Dasgupta, R., Raymond, S.N., Deienno, R., Bitsch, B., Isella, A. 2022. Planetesimal rings as the cause of the Solar System's planetary architecture. Nature Astronomy 6, 357–366. doi:10.1038/s41550-021-01557-zMarschall, R., Morbidelli, A. 2023. An inflationary disk phase to explain extended protoplanetary dust disks. Astronomy and Astrophysics 677. doi:10.1051/0004-6361/202346616Nesvorný, D., Roig, F.V., Deienno, R., 2021. The Role of Early Giant-planet Instability in Terrestrial Planet Formation. 161, 50. doi:10.3847/1538-3881/abc8efWoo, J.M.Y., Morbidelli, A., Grimm, S.L., Stadel, J., Brasser, R., 2023. Terrestrial planet formation from a ring. 396, 115497. doi:10.1016/j. icarus.2023.115497Woo, J.M.Y., Nesvorný, D., Scora, J.,Morbidelli, A., 2024. Terrestrial planet formation from a ring: Long-term simulations accounting for the giant planet instability. 417, 116109. doi:10.1016/j.icarus.2024.116109Broz, M., Chrenko, O., Nesvorny, D., Dauphas, N. 2021. Early terrestrial planet formation by torque-driven convergent migration of planetary embryos. Nature Astronomy 5, 898–902. doi:10.1038/s41550-021-01383-3Rubie, D.C., Frost, D.J., Mann, U., Asahara, Y., Nimmo, F., Tsuno, K., Kegler, P., Holzheid, A., Palme, H., 2011. Heterogeneous accretion, composition and core-mantle differentiation of the Earth. Earth and Planetary Science Letters 301, 31–42. doi:10.1016/j.epsl.2010.11.030.Dale, K.I., Morbidelli, A., Nathan, G., Woo, J., Nesvorný, D. and Rubie, D.C. Oxidation Constraints on Terrestrial Planet Formation from a Ring. Icarus, submitted.

Abstract Introduction Safety and efficacy of once-nightly sodium oxybate (ON-SXB; LUMRYZ™) were investigated in the phase 3 REST-ON trial (NCT02720744). Results demonstrated statistically significant improvements in the secondary endpoint of excessive daytime sleepiness (EDS) measured using the Epworth Sleepiness Scale (ESS; P< 0.001 vs placebo) at all doses tested beginning at week 2 (post hoc analysis, ON-SXB 6 g vs placebo at week 2). The objective of this post hoc analysis was to assess the magnitude of improvement in the patient-reported outcome of EDS following treatment with ON-SXB. Methods Participants aged ≥16 years with narcolepsy type 1 (NT1) or 2 (NT2) were randomized 1:1 to ON-SXB or placebo. Doses were 4.5 g week 1; 6 g weeks 2−3; 7.5 g weeks 4−8; and 9 g weeks 9−13. Median (interquartile range [IQR]) ESS scores were assessed for each dosing period. Results Mean age of participants was 31.2 years, 68% were female, 75.5% were white, and 76.4% had NT1. The modified intent-to-treat population included 190 participants (ON-SXB, n=97; placebo, n=93). Baseline median (IQR) ESS scores were 17 (14−19) for ON-SXB and 18 (15−21) for placebo. At week 1, median (IQR) ESS scores were 16 (12−18) for ON-SXB 4.5 g vs 17 (13−20) for placebo. At week 3 (ON-SXB 6 g), median (IQR) ESS scores were 14 (10−18) vs 17 (14−20) for placebo. At week 8 (ON-SXB 7.5 g), median (IQR) ESS scores were 12 (8−16) vs 15.5 (12−20) for placebo. At week 13, median (IQR) ESS scores for ON-SXB 9.0 g were 9.5 (6.0−15.0) vs 15 (11−19) for placebo. Conclusion Treatment with ON-SXB resulted in clinically meaningful improvements in EDS with doses ≥6 g, as median ESS scores were within the range considered normal (≤10) at the end of the trial. ON-SXB is considered an effective intervention in treatment of EDS for patients with narcolepsy with a once-at-bedtime dose. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Social jetlag (SJL), defined as the weekend-weekday discrepancy in the midpoint of the nocturnal sleep episode, is indicative of circadian misalignment. In adolescents, SJL is associated with poor sleep quality and impaired daytime and academic functioning. However, data on the prevalence and impact of SJL in preschoolers is limited. The present study examines the prevalence of SJL in preschoolers and its association with sleep, sleepiness, and developmental outcomes. Methods Data consisted of a cross-sectional sample of 841 children aged 2-5 years (M = 3.6 years, 50.3% female, 27.7% Black) in Mississippi between 2001-2003. Parents completed a questionnaire about child demographics, sleep habits, and developmental history. In a sub-sample of preschoolers, linear regression was used to examine the relationship between SJL and (i) measures of sleep quality (Children’s Sleep Wake Scale (CSWS)); (ii) daytime sleepiness (propensity to fall asleep), (iii) school readiness (Bracken School Readiness Assessment (BSRA)), and (iv) social skills (Social Skills Rating System (SSRS)). Results Following exploratory analysis, the prevalence of SJL within the sample was categorized as: no SJL (25.1%), < 90 mins of SJL (58.6%), and >90 mins of SJL (13.6%). Compared to no SJL and < 90 mins of SJL, >90 mins of SJL was associated with greater problems “going to bed” (R² = 0.012, F = 3.5, p = 0.031) and “returning to wakefulness” (R² = 0.092, F = 21.0, p < 0.001) on the CSWS. Additionally, >90 mins of SJL was associated with greater daytime sleepiness (R² = 0.097, F = 22.0, p < 0.001), relatively lower school readiness (R² = 0.075, F = 4.1, p = 0.020), and poorer social skills (R² = 0.054, F = 8.2, p < 0.001). Conclusion Social jetlag is highly prevalent among preschool children. Greater than 90 mins of SJL may be a risk factor for impaired daytime functioning and poor developmental outcomes. Future research is needed to identify moderators and mediators of these relationships. These findings could inform health intervention programs targeting sleep in early childhood. Support (if any) NSF-BSC0079435, UH3-0D023313

Integrative and Complementary TherapiesVol. 29, No. 3 Optimum Health Throughout the Lifespan: A Clinical Conversation with David Minkoff, MD, and Robert Rountree, MDPublished Online:16 Jun 2023https://doi.org/10.1089/ict.2023.29073.dmiAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 29Issue 3Jun 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Optimum Health Throughout the Lifespan: A Clinical Conversation with David Minkoff, MD, and Robert Rountree, MD.Integrative and Complementary Therapies.Jun 2023.91-97.http://doi.org/10.1089/ict.2023.29073.dmiPublished in Volume: 29 Issue 3: June 16, 2023PDF download

<h3>Objective:</h3> This study aims to assess patient preference for once- vs twice-nightly oxybate dosing regimens and experiences with the second dose of twice-nightly, immediate-release (IR) oxybate. <h3>Background:</h3> IR oxybates require patients with narcolepsy to awaken for a second dose 2.5–4 hours after the bedtime dose. RESTORE, an ongoing open-label/switch study (NCT04451668), evaluates long-term safety/tolerability of investigational, extended-release once-nightly sodium oxybate (FT218; ON-SXB). <h3>Design/Methods:</h3> Participants aged ≥16 years with narcolepsy type 1 or 2 who completed the phase 3 REST-ON trial, were on stable-dose (≥1 month) IR oxybate, or were oxybate-naive were eligible. For those switching to ON-SXB, initial doses were equivalent/closest to the previous total IR oxybate dose/night; adjustments were allowed in 1.5-g increments/week. Switch participants completed the nocturnal adverse event (AE) questionnaire about their IR oxybate experience at baseline and preference questionnaire 3 months after switching to ON-SXB. Safety and dose titration data are presented separately. <h3>Results:</h3> RESTORE enrollment completed 30June2022. At the interim data cutoff (01July2022), 78 switch participants completed preference questionnaires; 130 completed nocturnal AE questionnaires. Preference for the ON-SXB dosing regimen was stated by 93.6% (73/78) of participants. On the nocturnal AE questionnaire, 65.4% (85/130) unintentionally missed their second IR oxybate dose in previous 3 months; of participants who intentionally and/or unintentionally missed the second dose, 80.2% (73/91) felt worse the next day. Second nightly IR oxybate doses were taken &gt;4 h after the first by 39.2% (51/130); 51.0% (26/51) were somewhat to extremely groggy/unsteady the next morning. The second dose was rated somewhat to extremely inconvenient for 70.8%. Second-dose-related anxiety (29.2%) and need for someone to wake them (23.1%) were also reported. Most (90.8% [118/130]) arose from bed when waking for the second dose; 9 had falls and 5 reported injuries. <h3>Conclusions:</h3> These data indicate patient preference for once-at-bedtime dosing and reveal the treatment burden of twice-nightly IR oxybate. <b>Disclosure:</b> Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz Pharma. Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Harmony biosciences. Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Eisai . Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Inspire. The institution of Dr. Roy has received research support from Jazz . The institution of Dr. Roy has received research support from Inspire. The institution of Dr. Roy has received research support from Avadel. Dr. Harsh has nothing to disclose. Akinyemi Ajayi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz Pharmaceutical. Akinyemi Ajayi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz Pharmaceutical. Dr. Stern has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avadel Pharmaceutical. Dr. Stern has received intellectual property interests from a discovery or technology relating to health care. Dr. Seiden has received personal compensation for serving as an employee of Avadel Pharmaceuticals. Dr. Seiden has received stock or an ownership interest from Avadel Pharmaceuticals. Dr. Dubow has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Paragon Biosciences. Dr. Dubow has stock in Avadel Pharmaceuticals. Miss Gudeman has received personal compensation for serving as an employee of Avadel Pharmaceuticals. Miss Gudeman has stock in Avadel Pharmaceuticals.

<h3>Objective:</h3> The objective of RESTORE (NCT04451668) is to assess the long-term safety and tolerability of once-nightly sodium oxybate (ON-SXB; FT218), an investigational extended-release formulation. Interim safety data are reported; dose titration and patient preference data are presented separately. <h3>Background:</h3> In the pivotal phase 3 REST-ON trial (NCT02720744), ON-SXB met its 3 coprimary efficacy endpoints for treatment of adults with narcolepsy (<i>P</i>&lt;0.001 vs placebo) and had a safety profile consistent with that of immediate-release (IR) SXB. RESTORE is an ongoing open-label extension/switch study. <h3>Design/Methods:</h3> Participants aged ≥16 years with narcolepsy type 1/2 who completed the REST-ON trial, were on stable-dose IR oxybate for ≥1 month, or were oxybate-naive were eligible to enroll in RESTORE. Initial ON-SXB doses are equivalent/closest to previous total nightly dose of IR oxybate (switch participants) or 4.5 g/night (other participants); weekly ON-SXB dose adjustments were allowed at 1.5 g/week increments (maximum, 9 g/night). Safety data for participants who received ≥1 dose of ON-SXB as of 01July2022 are reported. <h3>Results:</h3> This analysis includes 180 individuals (REST-ON participants, n=15 [8.3%]; oxybate-naive, n=35 [19.4%]; switch, n=130 [72.2%]; white, n=150 [83.3%]; female, n=122 [67.8%]; mean age, 35 y [range, 16–84]). Adverse events (AEs) were reported by 105 (58.3%) participants. Serious AEs were recorded in 3 participants (abscess; deep vein thrombosis; rib fracture and pneumothorax); all were deemed unrelated to ON-SXB and did not result in study discontinuation. Seventy-six (42.2%) participants reported an adverse drug reaction (ADR), ie, AE related/possibly related to ON-SXB. The most common ADRs (≥3%) were nausea (11.7%), somnolence (6.7%), headache (5%), enuresis (5%), somnambulism (3.9%), dizziness (3.9%), tremor (3.9%), and vomiting (3.3%). Six (3.3%) participants discontinued due to ADRs. <h3>Conclusions:</h3> Thus far in RESTORE, ON-SXB is generally well tolerated, and no new safety signals have been observed. If approved, ON-SXB will offer a once-nightly oxybate treatment option for adults with narcolepsy. <b>Disclosure:</b> Dr. Stern has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avadel Pharmaceutical. Dr. Stern has received intellectual property interests from a discovery or technology relating to health care. Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz Pharma. Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Harmony biosciences. Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Eisai . Dr. Roy has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Inspire. The institution of Dr. Roy has received research support from Jazz . The institution of Dr. Roy has received research support from Inspire. The institution of Dr. Roy has received research support from Avadel. Colin Shapiro has nothing to disclose. Dr. Harsh has nothing to disclose. Akinyemi Ajayi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz Pharmaceutical. Akinyemi Ajayi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Jazz Pharmaceutical. The institution of Dr. Ibrahim has received research support from Avadel. The institution of Dr. Ibrahim has received research support from NIH. Dr. Seiden has received personal compensation for serving as an employee of Avadel Pharmaceuticals. Dr. Seiden has received stock or an ownership interest from Avadel Pharmaceuticals. Dr. Dubow has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Paragon Biosciences. Dr. Dubow has stock in Avadel Pharmaceuticals. Miss Gudeman has received personal compensation for serving as an employee of Avadel Pharmaceuticals. Miss Gudeman has stock in Avadel Pharmaceuticals.

Jung used creative methods such as picture-making and active imagination to work with complexes and in particular trauma and dissociation. A clinical example of a 60-year-old woman demonstrates the benefits of using creative methods to work with issues linked to early life, such as somatic intrusions of early childhood trauma. Significant inner figures were delineated, including the original figure associated with the infantile dissociative split. The figures illustrated Jung's complex theory by making visible the nonverbal inner states that were initially feared and experienced as Other. Within an analytic relationship that included a working through, an innate creative process unfolded that permitted inner figures to become agents of change within her psyche. This paper highlights the value of Jung's complex theory and the use of creative methods when working with dissociation, regression and unformulated infantile states, even when the analysand is in the later stages of adulthood.

Abstract The Flexible Array of Radars and Mesonets (FARM) Facility is an extensive mobile/quickly deployable (MQD) multiple-Doppler radar and in situ instrumentation network. The FARM includes four radars: two 3-cm dual polarization, dual frequency (DPDF), Doppler on Wheels (DOW6/DOW7), the Rapid-Scan DOW (RSDOW), and a quickly deployable (QD) DPDF 5-cm C band on Wheels (COW). The FARM includes three mobile mesonet (MM) vehicles with 3.5-m masts, an array of rugged QD weather stations (PODNET), QD weather stations deployed on infrastructure such as light/power poles (POLENET), four disdrometers, six MQD upper-air sounding systems and a Mobile Operations and Repair Center (MORC). The FARM serves a wide variety of research/educational uses. Components have deployed to &gt;30 projects during 1995–2020 in the United States, Europe, and South America, obtaining pioneering observations of a myriad of small spatial- and temporal-scale phenomena including tornadoes, hurricanes, lake-effect snow storms, aircraft-affecting turbulence, convection initiation, microbursts, intense precipitation, boundary layer structures and evolution, airborne hazardous substances, coastal storms, wildfires and wildfire suppression efforts, weather modification effects, and mountain/alpine winds and precipitation. The radars and other FARM systems support innovative educational efforts, deploying &gt;40 times to universities/colleges, providing hands-on access to cutting-edge instrumentation for their students. The FARM provides integrated multiple radar, mesonet, sounding, and related capabilities enabling diverse and robust coordinated sampling of three-dimensional vector winds, precipitation, and thermodynamics increasingly central to a wide range of mesoscale research. Planned innovations include S-band on Wheels Network (SOWNET) and Bistatic Adaptable Radar Network (BARN), offering more qualitative improvements to the field project observational paradigm, providing broad, flexible, and inexpensive 10-cm radar coverage and vector wind field measurements.