Nurses\u27 Alumnae Association Bulletin, April 1959

Alumnae News Anniversary Class of /34 Article from Pennsylvania Nurse Committee Reports Current Events at Jefferson Greetings from the President Jefferson Story Lost Members Letter - Past President Marriages Necrology New Arrivals Notices Pictured - Student Nurses\u27 Residence Report of the School of Nursing and Nursing Services Staff Nurses Social Functions Student Activities Voluntary Service Year of Great Activity and Expansio

Regularized Maximum Likelihood Image Synthesis and Validation for ALMA Continuum Observations of Protoplanetary Disks

Regularized Maximum Likelihood (RML) techniques are a class of image synthesis methods that achieve better angular resolution and image fidelity than traditional methods like CLEAN for sub-mm interferometric observations. To identify best practices for RML imaging, we used the GPU-accelerated open source Python package MPoL, a machine learning-based RML approach, to explore the influence of common RML regularizers (maximum entropy, sparsity, total variation, and total squared variation) on images reconstructed from real and synthetic ALMA continuum observations of protoplanetary disks. We tested two different cross-validation (CV) procedures to characterize their performance and determine optimal prior strengths, and found that CV over a coarse grid of regularization strengths easily identifies a range of models with comparably strong predictive power. To evaluate the performance of RML techniques against a ground truth image, we used MPoL on a synthetic protoplanetary disk dataset and found that RML methods successfully resolve structures at fine spatial scales present in the original simulation. We used ALMA DSHARP observations of the protoplanetary disk around HD 143006 to compare the performance of MPoL and CLEAN, finding that RML imaging improved the spatial resolution of the image by up to a factor of 3 without sacrificing sensitivity. We provide general recommendations for building an RML workflow for image synthesis of ALMA protoplanetary disk observations, including effective use of CV. Using these techniques to improve the imaging resolution of protoplanetary disk observations will enable new science, including the detection of protoplanets embedded in disks.Comment: 27 pages, 12 figures, accepted for publication in PAS

COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal

The COPI coat forms transport vesicles from the Golgi complex and plays a poorly defined role in endocytic trafficking. Here we show that COPI binds K63-linked polyubiquitin and this interaction is crucial for trafficking of a ubiquitinated yeast SNARE (Snc1). Snc1 is a v-SNARE that drives fusion of exocytic vesicles with the plasma membrane, and then recycles through the endocytic pathway to the Golgi for reuse in exocytosis. Removal of ubiquitin from Snc1, or deletion of a β’-COP subunit propeller domain that binds K63-linked polyubiquitin, disrupts Snc1 recycling causing aberrant accumulation in internal compartments. Moreover, replacement of the β’-COP propeller domain with unrelated ubiquitin-binding domains restores Snc1 recycling. These results indicate that ubiquitination, a modification well known to target membrane proteins to the lysosome or vacuole for degradation, can also function as recycling signal to sort a SNARE into COPI vesicles in a non-degradative pathway

Genetic risk scores associated with baseline lipoprotein subfraction concentrations do not associate with their responses to fenofibrate

Lipoprotein subclass concentrations are modifiable markers of cardiovascular disease risk. Fenofibrate is known to show beneficial effects on lipoprotein subclasses, but little is known about the role of genetics in mediating the responses of lipoprotein subclasses to fenofibrate. A recent genomewide association study (GWAS) associated several single nucleotide polymorphisms (SNPs) with lipoprotein measures, and validated these associations in two independent populations. We used this information to construct genetic risk scores (GRSs) for fasting lipoprotein measures at baseline (pre-fenofibrate), and aimed to examine whether these GRSs also associated with the responses of lipoproteins to fenofibrate. Fourteen lipoprotein subclass measures were assayed in 817 men and women before and after a three week fenofibrate trial. We set significance at a Bonferroni corrected alpha <0.05 (p < 0.004). Twelve subclass measures changed with fenofibrate administration (each p = 0.003 to <0.0001). Mixed linear models which controlled for age, sex, body mass index (BMI), smoking status, pedigree and study-center, revealed that GRSs were associated with eight baseline lipoprotein measures (p < 0.004), however no GRS was associated with fenofibrate response. These results suggest that the mechanisms for changes in lipoprotein subclass concentrations with fenofibrate treatment are not mediated by the genetic risk for fasting levels

An Exome-Wide Sequencing Study of Lipid Response to High-Fat Meal and Fenofibrate in Caucasians from the GOLDN Cohort

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting LDL cholesterol response to FFB (P = 1.24E-07), triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and triglyceride postprandial AUI response to FFB (P = 1.88E-06), respectively. We sought to replicate the association for SIPA1L2 in the Heredity and Phenotype Intervention (HAPI) Heart Study, which included a high-fat meal challenge but not FFB treatment. The associated rare variants in GOLDN were not observed in the HAPI Heart study, and thus the gene-based result was not replicated. For functional validation, we found that gene transcript level of SIPA1L2 is associated with triglyceride postprandial AUI (P \u3c 0.05) in GOLDN. Our study suggests unique genetic mechanisms contributing to the lipid response to the high-fat meal challenge and FFB therapy

Association of prenatal modifiable risk factors with attention-deficit hyperactivity disorder outcomes at age 10 and 15 in an extremely low gestational age cohort

BackgroundThe increased risk of developing attention-deficit hyperactivity disorder (ADHD) in extremely preterm infants is well-documented. Better understanding of perinatal risk factors, particularly those that are modifiable, can inform prevention efforts.MethodsWe examined data from the Extremely Low Gestational Age Newborns (ELGAN) Study. Participants were screened for ADHD at age 10 with the Child Symptom Inventory-4 (N = 734) and assessed at age 15 with a structured diagnostic interview (MINI-KID) to evaluate for the diagnosis of ADHD (N = 575). We studied associations of pre-pregnancy maternal body mass index (BMI), pregestational and/or gestational diabetes, maternal smoking during pregnancy (MSDP), and hypertensive disorders of pregnancy (HDP) with 10-year and 15-year ADHD outcomes. Relative risks were calculated using Poisson regression models with robust error variance, adjusted for maternal age, maternal educational status, use of food stamps, public insurance status, marital status at birth, and family history of ADHD. We defined ADHD as a positive screen on the CSI-4 at age 10 and/or meeting DSM-5 criteria at age 15 on the MINI-KID. We evaluated the robustness of the associations to broadening or restricting the definition of ADHD. We limited the analysis to individuals with IQ ≥ 70 to decrease confounding by cognitive functioning. We evaluated interactions between maternal BMI and diabetes status. We assessed for mediation of risk increase by alterations in inflammatory or neurotrophic protein levels in the first week of life.ResultsElevated maternal BMI and maternal diabetes were each associated with a 55–65% increase in risk of ADHD, with evidence of both additive and multiplicative interactions between the two exposures. MSDP and HDP were not associated with the risk of ADHD outcomes. There was some evidence for association of ADHD outcomes with high levels of inflammatory proteins or moderate levels of neurotrophic proteins, but there was no evidence that these mediated the risk associated with maternal BMI or diabetes.ConclusionContrary to previous population-based studies, MSDP and HDP did not predict ADHD outcomes in this extremely preterm cohort, but elevated maternal pre-pregnancy BMI, maternal diabetes, and perinatal inflammatory markers were associated with increased risk of ADHD at age 10 and/or 15, with positive interaction between pre-pregnancy BMI and maternal diabetes

NEID Reveals that The Young Warm Neptune TOI-2076 b Has a Low Obliquity

TOI-2076 b is a sub-Neptune-sized planet ($R=2.39 \pm 0.10 \mathrm{R_\oplus}$) that transits a young ($204 \pm 50 \mathrm{MYr}$) bright ($V = 9.2$) K-dwarf hosting a system of three transiting planets. Using spectroscopic observations with the NEID spectrograph on the WIYN 3.5 m Telescope, we model the Rossiter-McLaughlin effect of TOI-2076 b, and derive a sky-projected obliquity of $\lambda=-3_{-15}^{+16\:\circ}$. Using the size of the star ($R=0.775 \pm0.015 \mathrm{R_\odot}$), and the stellar rotation period ($P_{\mathrm{rot}}=7.27\pm0.23$ days), we estimate a true obliquity of $\psi=18_{-9}^{+10\:\circ}$ ($\psi < 34^\circ$ at 95% confidence), demonstrating that TOI-2076 b is on a well-aligned orbit. Simultaneous diffuser-assisted photometry from the 3.5 m Telescope at Apache Point Observatory rules out flares during the transit. TOI-2076 b joins a small but growing sample of young planets in compact multi-planet systems with well-aligned orbits, and is the fourth planet with an age $\lesssim 300$ Myr in a multi-transiting system with an obliquity measurement. The low obliquity of TOI-2076 b and the presence of transit timing variations in the system suggest the TOI-2076 system likely formed via convergent disk migration in an initially well-aligned disk.Comment: Submitted to ApJL, 13 pages, 4 figures, 3 table

The unusual M-dwarf Warm Jupiter TOI-1899~b: Refinement of orbital and planetary parameters

TOI-1899~b is a rare exoplanet, a temperate Warm Jupiter orbiting an M-dwarf, first discovered by \citet{Canas2020_toi1899} from a TESS single-transit event. Using new radial velocities (RVs) from the precision RV spectrographs HPF and NEID, along with additional TESS photometry and ground-based transit follow-up, we are able to derive a much more precise orbital period of $P = 29.090312_{-0.000035}^{+0.000036}$~d, along with a radius of $R_p = 0.99\pm0.03$~\unit{R_{J}}. We have also improved the constraints on planet mass, $M_p = 0.67\pm{0.04}$~\unit{M_{J}}, and eccentricity, which is consistent with a circular orbit at 2$\sigma$ ($e = 0.044_{-0.027}^{+0.029}$). TOI-1899~b occupies a unique region of parameter space as the coolest known ($T_{eq} \approx$ 380~K) Jovian-sized transiting planet around an M-dwarf; we show that it has great potential to provide clues regarding the formation and migration mechanisms of these rare gas giants through transmission spectroscopy with JWST as well as studies of tidal evolution.Comment: 19 pages, 7 figures, 3 tables, submitted to AJ (comments welcome