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1006 Background: T-DXd is approved for use in pts with HER2+ unresectable or mBC after a prior anti-HER2-based regimen in the metastatic or (neo)adjuvant setting, based on the randomized phase 3 DESTINY-Breast03 study (Cortes et al. N Engl J Med 2022). Older pts with HER2+ mBC tend to have worse efficacy and safety outcomes, regardless of treatment (Evans et al. Cancer Res 2021). Outcomes of older pts treated with T-DXd have not been thoroughly examined. Here we report age-specific (<65 vs ≥65 years) efficacy and pooled safety analyses of T-DXd from DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03. Methods: DESTINY-Breast01 (data cutoff [DCO], March 26, 2021) and DESTINY-Breast02 (DCO, June 30, 2022) enrolled pts whose disease progressed on trastuzumab emtansine (T-DM1); DESTINY-Breast02 compared T-DXd to chemotherapy of physician’s choice. DESTINY-Breast03 (DCO, July 25, 2022) included pts previously treated with trastuzumab and taxane; pts received either T-DXd or T-DM1. Results: At baseline, there were 44 (23.9%), 85 (20.9%), and 49 (18.8%) pts ≥65 years of age who received T-DXd in DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03, respectively. At DCO, median po

Destiny is a simple, direct, low cost mission to determine the properties of dark energy by obtaining a cosmologically deep supernova (SN) type Ia Hubble diagram. Operated at L2, its science instrument is a 1.65m space telescope, featuring a grism-fed near-infrared (NIR) (0.85-1.7micron) survey camera/spectrometer with a 0.12 square degree field of view. During its two-year primary mission, Destiny will detect, observe, and characterize ~3000 SN Ia events over the redshift interval 0.4&lt;z&lt;1.7 within a 3 square degree survey area. In conjunction with ongoing ground-based SN Ia surveys for z&lt;0.8, Destiny mission data will be used to construct a high-precision Hubble diagram and thereby constrain the dark energy equation of state from a time when it was strongly matter-dominated to the present when dark energy dominates. The grism-images simultaneously provide broad-band photometry, redshifts, and SN classification, as well as time-resolved diagnostic data for investigating additional SN luminosity diagnostics. Destiny will be used in its third year as a high resolution, wide-field imager to conduct a multicolor NIR weak lensing (WL) survey covering 1000 square degrees. The la

The majority of baryons, which account for $15\%$ of the matter in the Universe, will end their lives as carbon and oxygen inside cold black dwarfs. Dark matter (DM) makes up the remaining $85\%$ of the matter in the universe, however, the fate of DM is unknown. Here we show that the destiny of purely gravitationally interacting DM particles follows one of two possible routes. The first possible route, the "radiation-destiny" scenario, is that massive DM particles lose sufficient energy through gravitational radiation causing them to spiral into a supermassive black hole that ultimately disappears through Hawking radiation. The second possible route, the "drifting-alone" destiny, applies to lighter DM particles, where only the central DM halo region spirals into the central BH which is then Hawking radiated away. The rest of the DM halo is ripped apart by the accelerated expansion of the Universe.

DESTINY+ is an upcoming JAXA Epsilon medium-class mission to fly by the Geminids meteor shower parent body (3200) Phaethon. It will be the world's first spacecraft to escape from a near-geostationary transfer orbit into deep space using a low-thrust propulsion system. In doing so, DESTINY+ will demonstrate a number of technologies that include a highly efficient ion engine system, lightweight solar array panels, and advanced asteroid flyby observation instruments. These demonstrations will pave the way for JAXA's envisioned low-cost, high-frequency space exploration plans. Following the Phaethon flyby observation, DESTINY+ will visit additional asteroids as its extended mission. The mission design is divided into three phases: a spiral-shaped apogee-raising phase, a multi-lunar-flyby phase to escape Earth, and an interplanetary and asteroids flyby phase. The main challenges include the optimization of the many-revolution low-thrust spiral phase under operational constraints; the design of a multi-lunar-flyby sequence in a multi-body environment; and the design of multiple asteroid flybys connected via Earth gravity assists. This paper shows a novel, practical approach to tackle the

The JAXA/ISAS spacecraft DESTINY$^+$ will be launched to the active asteroid (3200) Phaethon in 2022. Among the proposed core payload is the DESTINY+ Dust Analyzer (DDA) which is an upgrade of the Cosmic Dust Analyzer flown on the Cassini spacecraft to Saturn (Srama et al. 2011). We use two up-to-date computer models, the ESA Interplanetary Meteoroid Engineering Model (IMEM, Dikarev et al. 2005), and the interstellar dust module of the Interplanetary Meteoroid environment for EXploration model (IMEX; Sterken2013 et al., Strub et al. 2019) to study the detection conditions and fluences of interplanetary and interstellar dust with DDA. Our results show that a statistically significant number of interplanetary and interstellar dust particles will be detectable with DDA during the 4-years interplanetary cruise of DESTINY+. The particle impact direction and speed can be used to descriminate between interstellar and interplanetary particles and likely also to distinguish between cometary and asteroidal particles.

The whites are the winning race, not only in North America. It is the tradition in the USA to call this phenomenon 'Manifest Destiny'. Christians used to believe that Jesus helped the Europeans to conquer the New World. Others refer to Darwinism and white supremacy. Critics put the blame on slavery, colonialism and apartheid. But all those ideologies fail to explain the magic of destiny. With good reason, the young USA was not based on Puritan ideas of a Christian Calvinist tyranny. Instead a humane state ideology was established, a mixture of belief in liberty, justice and human rights as well as in Manifest Destiny. This text looks in great detail at US-American history, and how the whites won the west, starting with dubious earliest traces of whites in the Americas. The text also gives answers to other destiny-related questions. A lot of typical stories, from the adventures of travellers to famous events of history, from the plots of Hollywood films to classical Shakespearean plays, helps to understand how destiny works. And this text only begins when destiny starts to become unexplainable or even unbelievable. The text also addresses the most basic issues of religion and philos

Social media has become a major communication channel for communities centered around video games. Consequently, social media offers a rich data source to study online communities and the discussions evolving around games. Towards this end, we explore a large-scale dataset consisting of over 1 million tweets related to the online multiplayer shooter Destiny and spanning a time period of about 14 months using unsupervised clustering and topic modelling. Furthermore, we correlate Twitter activity of over 3,000 players with their playtime. Our results contribute to the understanding of online player communities by identifying distinct player groups with respect to their Twitter characteristics, describing subgroups within the Destiny community, and uncovering broad topics of community interest.

DESTINY+ is an upcoming JAXA Epsilon medium-class mission to flyby multiple asteroids including Phaethon. As an asteroid flyby observation instrument, a telescope mechanically capable of single-axis rotation, named TCAP, is mounted on the spacecraft to track and observe the target asteroids during flyby. As in past flyby missions utilizing rotating telescopes, TCAP is also used as a navigation camera for autonomous optical navigation during the closest-approach phase. To mitigate the degradation of the navigation accuracy, past missions performed calibration of the navigation camera's alignment before starting optical navigation. However, such calibration requires significant operational time to complete and imposes constraints on the operation sequence. From the above background, the DESTINY+ team has studied the possibility of reducing operational costs by allowing TCAP alignment errors to remain. This paper describes an autonomous optical navigation algorithm robust to the misalignment of rotating telescopes, proposed in this context. In the proposed method, the misalignment of the telescope is estimated simultaneously with the spacecraft's orbit relative to the flyby target. To

To understand the formation of planetary systems, one needs to understand the initial conditions of planet formation, i.e. the young gas-rich planet forming disks. Spatially resolved high-contrast observations are of particular interest, since substructures in disks, linked to planet formation, can be detected and close companions or even planets in formation embedded in the disk can be revealed. In this study we present the first result of the DESTINYS survey (Disk Evolution Study Through Imaging of Nearby Young Stars). DESTINYS is an ESO/SPHERE large program that aims at studying disk evolution in scattered light, mainly focusing on a sample of low-mass stars (&lt;1$M_\odot$) in nearby (~200 pc) star-forming regions. In this particular study we present the observations of the ET Cha (RECX 15) system, a nearby 'old' classical T Tauri star (5-8 Myr, ~100 pc), which is still strongly accreting. We use SPHERE/IRDIS in H-band polarimetric imaging mode to obtain high contrast images of the ET Cha system to search for scattered light from the circumstellar disk as well as thermal emission from close companions. We additionally employ VLT/NACO total intensity archival data taken in 2003.

In DESTINY-Breast01 (NCT03248492) and DESTINY-Breast03 (NCT03529110), trastuzumab deruxtecan (T-DXd) demonstrated unprecedented activity in patients (pts) with HER2+ (immunohistochemistry 3+; immunohistochemistry 2+/in situ hybridization+) advanced metastatic breast cancer (mBC), leading to regulatory approvals in several countries for HER2+ unresectable/mBC after a prior anti–HER2-based regimen. DESTINY-Breast02 (NCT03523585) is a phase 3 trial of T-DXd vs treatment of physician’s choice (TPC) in patients with centrally confirmed HER2+ mBC previously treated with trastuzumab emtansine (T-DM1). It acts as a confirmatory study for the pivotal phase 2 DESTINY-Breast01 trial. Here we report the primary results of DESTINY-Breast02. Methods: Pts with HER2+ mBC were randomized 2:1 to receive T-DXd or TPC (trastuzumab + capecitabine or lapatinib + capecitabine) and stratified by hormone receptor (HR) status (HR+/HR-), prior pertuzumab treatment, and history of visceral disease. The primary endpoint of this time-driven primary analysis was progression-free survival (PFS) as determined by blinded independent central review (BICR). The powered secondary endpoint was overall survival (OS).

The recognition that the cosmological constant may be non-zero forces us to re-evaluate standard notions about the connection between geometry and the fate of our Universe. An open Universe can recollapse, and a closed Universe can expand forever. As a corollary, we point out that there is no set of cosmological observations we can perform that will unambiguously allow us to determine what the ultimate destiny of the Universe will be.

The binary systems consisting of a Be star and a white dwarf (BeWDs) are very interesting.They can originate from the binaries composed of a Be star and a subdwarf O or B star (BesdOBs), and they can merge into red giants via luminous red nova or can evolve into double WD potentially detected by $LISA$ mission. Using the method of population synthesis, we investigate the formation and the destiny of BeWDs,and discuss the effects of the metallicity ($Z$) and the common envelope evolution parameters. We find that BesdOBs are significant progenitors of BeWDs. About 30\% ($Z=0.0001$)-50\% ($Z=0.02$) of BeWDs come from BesdOBs. About 60\% ($Z=0.0001$) -70\% ($Z=0.02$) of BeWDs turn into red giants via a merger between a WD and a non-degenerated star. About 30\% ($Z=0.0001$) -40\% ($Z=0.02$) of BeWDs evolve into double WDs which are potential gravitational waves of $LISA$ mission at a frequency band between about $3\times10^{-3}$ and $3\times10^{-2}$ Hz. The common envelope evolution parameter introduces an uncertainty with a factor of about 1.3 on BeWD populations in our simulations.

During the querelle des infiniment petits, Leibniz wrote several texts to justify using Differential calculus among Parisian savants. However, only three were published. Among these publications, ''Sentiment de Monsieur Leibnitz'' had a peculiar destiny. Although we are aware of the manuscript (Gotha FB A 448--449, Bl. 41--42), it is only recently that we have identified a copy of its impression in the British Library catalogue. This copy was printed in 1706 together with writings by other mathematicians united in the defence of the new calculus -- Joseph Saurin, Jacob Hermann and the Bernoulli brothers. Recently published epistolary exchanges indicate that Jean-Paul Bignon, at the time director of the Royal Academy of Sciences, in order to calm down the institution, had prohibited this publication and confiscated the prints.This article examine the epistemological and institutional issues at stake in ''Sentiment de Monsieur Leibnitz''.

This study explores a novel approach to predicting key bug-related outcomes, including the time to resolution, time to fix, and ultimate status of a bug, using data from the Bugzilla Eclipse Project. Specifically, we leverage features available before a bug is resolved to enhance predictive accuracy. Our methodology incorporates sentiment analysis to derive both an emotionality score and a sentiment classification (positive or negative). Additionally, we integrate the bug's priority level and its topic, extracted using a BERTopic model, as features for a Convolutional Neural Network (CNN) and a Multilayer Perceptron (MLP). Our findings indicate that the combination of BERTopic and sentiment analysis can improve certain model performance metrics. Furthermore, we observe that balancing model inputs enhances practical applicability, albeit at the cost of a significant reduction in accuracy in most cases. To address our primary objectives, predicting time-to-resolution, time-to-fix, and bug destiny, we employ both binary classification and exact time value predictions, allowing for a comparative evaluation of their predictive effectiveness. Results demonstrate that sentiment analysis s

DESTINY+ is a planned JAXA medium-class Epsilon mission from Earth to deep space using a low-thrust, many-revolution orbit. Such a trajectory design is a challenging problem not only for trajectory design but also for flight operations, and in particular, it is essential to evaluate the impact of operational uncertainties to ensure mission success. In this study, we design the low-thrust trajectory from Earth orbit to a lunar transfer orbit by differential dynamic programming using the Sundman transformation. The results of Monte Carlo simulations with operational uncertainties confirm that the spacecraft can be successfully guided to the lunar transfer orbit by using the feedback control law of differential dynamic programming in the angular domain.

We report on the first polarimetric study of (3200) Phaethon, the target of JAXA's DESTINY$^+$ mission, in the negative branch to ensure its anhydrous nature and to derive an accurate geometric albedo. We conducted observations at low phase angles (Sun-target-observer angle, alpha = 8.8-32.4 deg) from 2021 October to 2022 January and found that Phaethon has a minimum polarization degree $P_{min}$ = -1.3 +- 0.1 %, a polarimetric slope h = 0.22 +- 0.02 % deg$^{-1}$, and an inversion angle alpha$_0$ = 19.9 +- 0.3 deg. The derived geometric albedo is $p_V$ = 0.11 (in the range of 0.08-0.13). These polarimetric properties are consistent with anhydrous chondrites, and contradict hydrous chondrites and typical cometary nuclei.

Thermophysical models allow for improved constraints on the physical and thermal surface properties of asteroids beyond what can be inferred from more simple thermal modeling, provided a sufficient number of observations is available. We present thermophysical modeling results of observations from the NEOWISE mission for two near-Earth asteroids which are the targets of the DESTINY+ flyby mission: (3200) Phaethon and (155140) 2005 UD. Our model assumes a rotating, cratered, spherical surface, and employs a Monte Carlo Markov Chain to explore the multi-dimensional parameter space of the fit. We find an effective spherical diameter for Phaethon of $4.6^{+0.2}_{-0.3}~$km, a geometric albedo of $p_V=0.16\pm0.02$, and a thermal inertia $Γ=880$ $^{+580}_{-330}$, using five epochs of NEOWISE observations. The best model fit for (155140) 2005 UD was less well constrained due to only having two NEOWISE observation epochs, giving a diameter of $1.2\pm0.4~$km and a geometric albedo of $p_V=0.14\pm0.09$.

Accurate estimation of brightness of (3200) Phaethon up to lower phase angles are essential for planning of the on-board camera of the DESTINY$^{+}$ mission. We have carried out intensive observations of Phaethon in the optical wavelength ($g$, $r$, and $i$) with the TriCCS camera on the Seimei 3.8 m telescope in October and November, 2021. We derived the absolute magnitude $H_\mathrm{V}$ and the slope parameter $G$ of Phaethon as $H_\mathrm{V}=14.23\pm0.02$ and $G=0.040\pm0.008$ from multiple photometric observations including lower phase angles down to $\sim$9$^{\circ}$ with the $H$-$G$ model. Using the $H_\mathrm{V}$ value and the geometric albedo of Phaethon derived in previous polarimetric studies, we estimated that the Phaethon's diameter is within a range of 5.22 to 6.74 km, which is consistent with radar and occultation observations. With the linear model, we derived $H_\mathrm{V}=14.65\pm0.02$, which corresponds to a diameter range of 4.30 to 5.56 km. Our simultaneous tricolor lightcurves of Phaethon indicate that no rotational spectral variations larger than 0.018 and 0.020 mag in the g-r and r-i colors, possibly related to inhomogeneity of the surface material and/or str

Most stars form as part of a stellar group. These young stars are mostly surrounded by a disk from which potentially a planetary system might form. Both, the disk and later on the planetary system, may be affected by the cluster environment due to close fly-bys. The here presented database can be used to determine the gravitational effect of such fly-bys on non-viscous disks and planetary systems. The database contains data for fly-by scenarios spanning mass ratios between the perturber and host star from 0.3 to 50.0, periastron distances from 30 au to 1000 au, orbital inclination from $0^{\circ}$ to ${180^\circ}$ and angle of periastron of $0^{\circ}$, ${45^\circ}$ and ${90^\circ}$. Thus covering a wide parameter space relevant for fly-bys in stellar clusters. The data can either be downloaded to perform one's own diagnostics like for e.g. determining disk size, disk mass, etc. after specific encounters, obtain parameter dependencies or the different particle properties can be visualized interactively. Currently the database is restricted to fly-bys on parabolic orbits, but it will be extended to hyperbolic orbits in the future. All of the data from this extensive parameter study

DESTINY-CRC01 (NCT03384940) was a multicentre, open-label, phase 2 study that investigated the safety and efficacy of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-expressing metastatic colorectal cancer (CRC). The present exploratory biomarker analysis aims to investigate relationships between biomarkers and clinical outcomes in patients with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+ and in situ hybridization [ISH] positive) Cohort A (N = 53) of DESTINY-CRC01. Higher levels of HER2 biomarkers in baseline tissue and liquid biopsies, including HER2 status (IHC/ISH), HER2/CEP17 ratio, HER2 ISH signals, HER2 H-score, plasma HER2 (ERBB2) amplification status, HER2 adjusted plasma copy number, and HER2 extracellular domain correlate with antitumor activity (indicated by objective response rate, progression-free survival, and overall survival) of T-DXd. Baseline circulating tumor DNA (ctDNA) analysis suggests antitumor activity of T-DXd in patients who had baseline activating RAS, PIK3CA, or HER2 mutations detected in ctDNA. The phase 2 trial, DESTINYCRC01, previously demonstrated durable activity of trastuzumab deruxtecan (T