A Differentially Private Weighted Empirical Risk Minimization Procedure and its Application to Outcome Weighted Learning

It is commonplace to use data containing personal information to build predictive models in the framework of empirical risk minimization (ERM). While these models can be highly accurate in prediction, results obtained from these models with the use of sensitive data may be susceptible to privacy attacks. Differential privacy (DP) is an appealing framework for addressing such data privacy issues by providing mathematically provable bounds on the privacy loss incurred when releasing information from sensitive data. Previous work has primarily concentrated on applying DP to unweighted ERM. We consider an important generalization to weighted ERM (wERM). In wERM, each individual's contribution to the objective function can be assigned varying weights. In this context, we propose the first differentially private wERM algorithm, backed by a rigorous theoretical proof of its DP guarantees under mild regularity conditions. Extending the existing DP-ERM procedures to wERM paves a path to deriving privacy-preserving learning methods for individualized treatment rules, including the popular outcome weighted learning (OWL). We evaluate the performance of the DP-wERM application to OWL in a simulation study and in a real clinical trial of melatonin for sleep health. All empirical results demonstrate the viability of training OWL models via wERM with DP guarantees while maintaining sufficiently useful model performance. Therefore, we recommend practitioners consider implementing the proposed privacy-preserving OWL procedure in real-world scenarios involving sensitive data.Comment: 24 pages and 2 figures for the main manuscript, 5 pages and 2 figures for the supplementary material

Neurologic Morbidity and Functional Independence in Adult Survivors of Childhood Cancer

OBJECTIVE: To examine associations between neurologic late effects and attainment of independence in adult survivors of childhood cancer treated with central nervous system (CNS)-directed therapies. METHODS: A total of 7881 survivors treated with cranial radiation therapy (n = 4051; CRT) and/or intrathecal methotrexate (n = 4193; IT MTX) ([CNS-treated]; median age [range] = 25.5 years [18-48]; time since diagnosis = 17.7 years [6.8-30.2]) and 8039 without CNS-directed therapy reported neurologic conditions including stroke, seizure, neurosensory deficits, focal neurologic dysfunction, and migraines/severe headaches. Functional independence was assessed using latent class analysis with multiple indicators (independent living, assistance with routine and personal care needs, ability to work/attend school, attainment of driver\u27s license, marital/partner status). Multivariable regression models, adjusted for age, sex, race/ethnicity, and chronic health conditions, estimated odds ratios (OR) or relative risks (RR) for associations between neurologic morbidity, functional independence, and emotional distress. RESULTS: Among CNS-treated survivors, three classes of independence were identified: (1) moderately independent, never married, and non-independent living (78.7%); (2) moderately independent, unable to drive (15.6%); and (3) non-independent (5.7%). In contrast to 50% of non-CNS-treated survivors and 60% of siblings, a fourth fully independent class of CNS-treated survivors was not identified. History of stroke (OR = 2.50, 95% CI: 1.70-3.68), seizure (OR = 9.70, 95% CI: 7.37-12.8), neurosensory deficits (OR = 2.67, 95% CI: 2.16-3.31), and focal neurologic dysfunction (OR = 3.05, 95% CI: 2.40-3.88) were associated with non-independence among CNS-treated survivors. Non-independence was associated with emotional distress symptoms. INTERPRETATION: CNS-treated survivors do not attain full independence comparable to non-CNS-treated survivors or siblings. Interventions to promote independence may be beneficial for survivors with treatment-related neurological sequalae

Inequalities in vaccination coverage for young females whose parents are informal caregivers

The effects of caregiver strain and stress on preventive health service utilization among adult family members are well-established, but the effects of informal caregiving on children of caregivers are unknown. We aimed to assess whether inequalities in vaccination coverage (specifically human papillomavirus [HPV] and influenza) exist for females aged 9 to 17 years whose parents are informal caregivers (i.e., care providers for family members or others who are not functionally independent) compared with females whose parents are not informal caregivers. Data from the 2009 Behavioral Risk Factor Surveillance System were analyzed using Poisson regression with robust variance to estimate overall and subgroup-specific HPV and influenza vaccination prevalence ratios (PRs) and corresponding 95% confidence limits (CL) comparing females whose parents were informal caregivers with females whose parents were not informal caregivers. Our unweighted study populations comprised 1645 and 1279 females aged 9 to 17 years for the HPV and influenza vaccination analyses, respectively. Overall, both HPV and influenza vaccination coverage were lower among females whose parents were informal caregivers (HPV: PR = 0.72, 95% CL: 0.53, 0.97; Influenza: PR = 0.89, 95% CL: 0.66, 1.2). Our results suggest consistently lower HPV and influenza vaccination coverage for young females whose parents are informal caregivers. Our study provides new evidence about the potential implications of caregiving on the utilization of preventive health services among children of caregivers

The TESS-Keck Survey. XV. Precise Properties of 108 TESS Planets and Their Host Stars

We present the stellar and planetary properties for 85 TESS Objects of Interest (TOIs) hosting 108 planet candidates which comprise the TESS-Keck Survey (TKS) sample. We combine photometry, high-resolution spectroscopy, and Gaia parallaxes to measure precise and accurate stellar properties. We then use these parameters as inputs to a lightcurve processing pipeline to recover planetary signals and homogeneously fit their transit properties. Among these transit fits, we detect significant transit-timing variations among at least three multi-planet systems (TOI-1136, TOI-1246, TOI-1339) and at least one single-planet system (TOI-1279). We also reduce the uncertainties on planet-to-star radius ratios $R_p/R_\star$ across our sample, from a median fractional uncertainty of 8.8$\%$ among the original TOI Catalog values to 3.0$\%$ among our updated results. With this improvement, we are able to recover the Radius Gap among small TKS planets and find that the topology of the Radius Gap among our sample is broadly consistent with that measured among Kepler planets. The stellar and planetary properties presented here will facilitate follow-up investigations of both individual TOIs and broader trends in planet properties, system dynamics, and the evolution of planetary systems.Comment: Accepted at The Astronomical Journal; 21 pages, 9 figure

The TESS-Keck Survey. XII. A Dense 1.8 R ⊕ Ultra-short-period Planet Possibly Clinging to a High-mean-molecular-weight Atmosphere after the First Gigayear

The extreme environments of ultra-short-period planets (USPs) make excellent laboratories to study how exoplanets obtain, lose, retain, and/or regain gaseous atmospheres. We present the confirmation and characterization of the USP TOI-1347 b, a 1.8±0.1 R⊕ planet on a 0.85 day orbit that was detected with photometry from the TESS mission. We measured radial velocities of the TOI-1347 system using Keck/HIRES and HARPS-N and found the USP to be unusually massive at 11.1±1.2 M⊕. The measured mass and radius of TOI-1347 b imply an Earth-like bulk composition. A thin H/He envelope (>0.01% by mass) can be ruled out at high confidence. The system is between 1 and 1.8 Gyr old; therefore, intensive photoevaporation should have concluded. We detected a tentative phase curve variation (3σ) and a secondary eclipse (2σ) in TESS photometry, which if confirmed could indicate the presence of a high-mean-molecular-weight atmosphere. We recommend additional optical and infrared observations to confirm the presence of an atmosphere and investigate its composition

The TESS-Keck Survey XVII: Precise Mass Measurements in a Young, High Multiplicity Transiting Planet System using Radial Velocities and Transit Timing Variations

We present a radial velocity (RV) analysis of TOI-1136, a bright TESS system with six confirmed transiting planets, and a seventh single-transiting planet candidate. All planets in the system are amenable to transmission spectroscopy, making TOI-1136 one of the best targets for intra-system comparison of exoplanet atmospheres. TOI-1136 is young ($\sim$ 700 Myr), and the system exhibits transit timing variations (TTVs). The youth of the system contributes to high stellar variability on the order of 50 m s$^{-1}$, much larger than the likely RV amplitude of any of the transiting exoplanets. Utilizing 359 HIRES and APF RVs collected as a part of the TESS-Keck Survey (TKS), and 51 HARPS-N RVs, we experiment with a joint TTV-RV fit. With seven possible transiting planets, TTVs, more than 400 RVs, and a stellar activity model, we posit that we may be presenting the most complex mass recovery of an exoplanet system in the literature to date. By combining TTVs and RVs, we minimized GP overfitting and retrieved new masses for this system: (m$_{b-g}$ = 3.50$^{+0.8}_{-0.7}$, 6.32$^{+1.1}_{-1.3}$, 8.35$^{+1.8}_{-1.6}$, 6.07$^{+1.09}_{-1.01}$, 9.7$^{+3.9}_{-3.7}$, 5.6$^{+4.1}_{-3.2}$ M$_{\oplus}$). We are unable to significantly detect the mass of the seventh planet candidate in the RVs, but we are able to loosely constrain a possible orbital period near 80 days. Future TESS observations might confirm the existence of a seventh planet in the system, better constrain the masses and orbital properties of the known exoplanets, and generally shine light on this scientifically interesting system.Comment: Accepted for publication in the Astronomical Journa

The TESS-Keck Survey. XXII. A Sub-Neptune Orbiting TOI-1437

Exoplanet discoveries have revealed a dramatic diversity of planet sizes across a vast array of orbital architectures. Sub-Neptunes are of particular interest; due to their absence in our own solar system, we rely on demographics of exoplanets to better understand their bulk composition and formation scenarios. Here, we present the discovery and characterization of TOI-1437 b, a sub-Neptune with a 18.84 day orbit around a near-solar analog (M⋆ = 1.10 ± 0.10 M☉, R⋆=1.17 ± 0.12 R☉). The planet was detected using photometric data from the Transiting Exoplanet Survey Satellite (TESS) mission and radial velocity (RV) follow-up observations were carried out as a part of the TESS-Keck Survey using both the HIRES instrument at Keck Observatory and the Levy Spectrograph on the Automated Planet Finder telescope. A combined analysis of these data reveal a planet radius of Rp = 2.24 ± 0.23 R⊕ and a mass measurement of Mp = 9.6 ± 3.9 M⊕). TOI-1437 b is one of few (∼50) known transiting sub-Neptunes orbiting a solar-mass star that has a RV mass measurement. As the formation pathway of these worlds remains an unanswered question, the precise mass characterization of TOI-1437 b may provide further insight into this class of planet

The TESS-Keck Survey. XVI. Mass Measurements for 12 Planets in Eight Systems

With JWST's successful deployment and unexpectedly high fuel reserves, measuring the masses of sub-Neptunes transiting bright, nearby stars will soon become the bottleneck for characterizing the atmospheres of small exoplanets via transmission spectroscopy. Using a carefully curated target list and more than two years' worth of APF-Levy and Keck-HIRES Doppler monitoring, the TESS-Keck Survey is working toward alleviating this pressure. Here we present mass measurements for 11 transiting planets in eight systems that are particularly suited to atmospheric follow-up with JWST. We also report the discovery and confirmation of a temperate super-Jovian-mass planet on a moderately eccentric orbit. The sample of eight host stars, which includes one subgiant, spans early-K to late-F spectral types ($T_\mathrm{eff} =$ 5200--6200 K). We homogeneously derive planet parameters using a joint photometry and radial velocity modeling framework, discuss the planets' possible bulk compositions, and comment on their prospects for atmospheric characterization.Comment: Accepted for publication in The Astronomical Journal on 2023-Jun-22. 60 pages, 17 Tables, 28 Figure

Bacterial Cyclic Diguanylate Signaling Networks Sense Temperature

Many bacteria use the second messenger cyclic diguanylate (c-di-GMP) to control motility, biofilm production and virulence. Here, we identify a thermosensory diguanylate cyclase (TdcA) that modulates temperature-dependent motility, biofilm development and virulence in the opportunistic pathogen Pseudomonas aeruginosa. TdcA synthesizes c-di-GMP with catalytic rates that increase more than a hundred-fold over a ten-degree Celsius change. Analyses using protein chimeras indicate that heat-sensing is mediated by a thermosensitive Per-Arnt-SIM (PAS) domain. TdcA homologs are widespread in sequence databases, and a distantly related, heterologously expressed homolog from the Betaproteobacteria order Gallionellales also displayed thermosensitive diguanylate cyclase activity. We propose, therefore, that thermotransduction is a conserved function of c-di-GMP signaling networks, and that thermosensitive catalysis of a second messenger constitutes a mechanism for thermal sensing in bacteria

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts