Changing antiepilepsy drug-prescribing trends in women with epilepsy in the UK and Ireland and the impact on major congenital malformations

Objectives: After 20 years of data collection, pregnancy registers have informed prescribing practice. Various populations show trends for a reduction in valproate prescribing, which is associated with an increased risk of anatomical teratogenesis and neurodevelopmental effects in those exposed in utero. Our aim was to determine if any shifts in prescribing trends have occurred in the UK and Ireland Epilepsy and Pregnancy Register cohort and to assess if there had been any change in the overall major congenital malformation (MCM) rate over time. Methods: The UK and Ireland Epilepsy and Pregnancy Register, a prospective, observational, registration and follow-up study established in 1996, was used to determine the changes in antiepileptic drugs (AEDs) utilised during pregnancy and the MCM rate between 1996 and 2016. Linear regression analysis was used to assess changes in AED utilisation, and Poisson regression was used for the analysis of trends in the MCM rates. Results: Outcome data for 9247 pregnancies showed a stable percentage of monotherapy to polytherapy prescribing habits over time. After Bonferroni correction, statistically significant (p<0.003) changes were found in monotherapy prescribing with increases in lamotrigine and levetiracetam and decreases in valproate and carbamazepine use. Between 1996 and 2016, the total MCM rate showed a 2.1% reduction per year (incidence risk ratio 0.979 (95% CIs 0.956 to 1.002) but Poisson regression analysis showed that this was not statistically significant p=0.08). Conclusion: Significant changes are seen in the prescribing habits in this cohort over 20 years, but a statistically significant change in the MCM rate was not detected. This work should be replicated on a larger scale to determine if significant changes are occurring in the MCM rate, which would allow a robust economic estimate of the benefits of improvements in prescribing practice and the personal effect of such changes

Impact of socioeconomic status on cancer incidence and stage at diagnosis: selected findings from the surveillance, epidemiology, and end results: National Longitudinal Mortality Study

BACKGROUND: Population-based cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) Program at the National Cancer Institute (NCI) are mainly based on medical records and administrative information. Individual-level socioeconomic data are not routinely reported by cancer registries in the United States because they are not available in patient hospital records. The U.S. representative National Longitudinal Mortality Study (NLMS) data provide self-reported, detailed demographic and socioeconomic data from the Social and Economic Supplement to the Census Bureau's Current Population Survey (CPS). In 1999, the NCI initiated the SEER-NLMS study, linking the population-based SEER cancer registry data to NLMS data. The SEER-NLMS data provide a new unique research resource that is valuable for health disparity research on cancer burden. We describe the design, methods, and limitations of this data set. We also present findings on cancer-related health disparities according to individual-level socioeconomic status (SES) and demographic characteristics for all cancers combined and for cancers of the lung, breast, prostate, cervix, and melanoma. METHODS: Records of cancer patients diagnosed in 1973–2001 when residing 1 of 11 SEER registries were linked with 26 NLMS cohorts. The total number of SEER matched cancer patients that were also members of an NLMS cohort was 26,844. Of these 26,844 matched patients, 11,464 were included in the incidence analyses and 15,357 in the late-stage diagnosis analyses. Matched patients (used in the incidence analyses) and unmatched patients were compared by age group, sex, race, ethnicity, residence area, year of diagnosis, and cancer anatomic site. Cohort-based age-adjusted cancer incidence rates were computed. The impact of socioeconomic status on cancer incidence and stage of diagnosis was evaluated. RESULTS: Men and women with less than a high school education had elevated lung cancer rate ratios of 3.01 and 2.02, respectively, relative to their college educated counterparts. Those with family annual incomes less than $12,500 had incidence rates that were more than 1.7 times the lung cancer incidence rate of those with incomes$50,000 or higher. Lower income was also associated with a statistically significantly increased risk of distant-stage breast cancer among women and distant-stage prostate cancer among men. CONCLUSIONS: Socioeconomic patterns in incidence varied for specific cancers, while such patterns for stage were generally consistent across cancers, with late-stage diagnoses being associated with lower SES. These findings illustrate the potential for analyzing disparities in cancer outcomes according to a variety of individual-level socioeconomic, demographic, and health care characteristics, as well as by area measures available in the linked database

Myelomatosis with type III hyperlipoproteinemia - clinical and metabolic studies

We investigated the metabolism of intermediate-density lipoproteins (IDL [1.006 to 1.019 g per milliliter]) and low-density lipoproteins (LDL [1.019 to 1.063 g per milliliter]) in two men with Type III hyperlipoproteinemia associated with myelomatosis. In vivo kinetic studies using Radio-labeled autologous lipoproteins demonstrated a greatly reduced fractional catabolic rate of IDL, relative to control values (patients vs. normal, 0.006 and 0.025 per hour vs. 0.20±0.08 per hour [mean ±S.E.M.]) and a greatly prolonged IDL-to-LDL conversion time (45 and 17 hours vs. 5.4±1.6 hours). In studies in vitro, LDL from both patients failed to bind to the LDL receptor of normal blood lymphocytes, whereas LDL from subjects with familial Type III hyperlipoproteinemia bound normally to the receptor. In one patient immunoglobulin was shown to be associated with IDL and LDL. Thus, hyperlipoproteinemia reflected an impaired metabolism of IDL, probably secondary to the binding of immunoglobulin to the lipoproteins. A similar impairment of receptor-mediated LDL catabolism did not elevate the plasma LDL concentration because of the low IDL-to-LDL conversion rate

Magellanic System Stars Identified in the SMACS J0723.3-7327 JWST ERO Images

We identify 68 distant stars in JWST/NIRCam ERO images of the field of galaxy cluster SMACS J0723.3-7327 (SMACS 0723). Given the relatively small ($\sim$$10^{\circ}$) angular separation between SMACS 0723 and the Large Magellanic Cloud, it is likely that these stars are associated with the LMC outskirts or Leading Arm. This is further bolstered by a spectral energy distribution analysis, which suggests an excess of stars at a physical distance of $40-100$ kpc, consistent with being associated with or located behind the Magellanic system. In particular, we find that the overall surface density of stars brighter than 27.0 mag in the field of SMACS 0723 is $\sim$2.3 times that of stars in a blank field with similar galactic latitude (the North Ecliptic Pole Time Domain Field), and that the density of stars in the SMACS 0723 field with SED-derived distances consistent with the Magellanic system is $\sim$7.3 times larger than that of the blank field. The candidate stars at these distances are consistent with a stellar population at the same distance modulus with [Fe/H] $= -1.0$ and an age of $\sim$$5.0$ Gyr. On the assumption that all of the 68 stars are associated with the LMC, then the stellar density of the LMC at the location of the SMACS 0723 field is $\sim$$710$ stars kpc$^{-3}$, which helps trace the density of stars in the LMC outskirts.Comment: Submitted to ApJ, comments welcom

JWST's PEARLS: TN J1338-1942 -- I. Extreme jet triggered star-formation in a z=4.11 luminous radio galaxy

We present the first JWST observations of the z = 4.11 luminous radio galaxy TN J1338–1942, obtained as part of the ‘Prime Extragalactic Areas for Reionization and Lensing Science’ (‘PEARLS’) project. Our NIRCam observations, designed to probe the key rest-frame optical continuum and emission line features at this redshift, enable resolved spectral energy distribution modelling that incorporates both a range of stellar population assumptions and radiative shock models. With an estimated stellar mass of log10(M/M) ∼ 10.9, TN J1338–1942 is confirmed to be one of the most massive galaxies known at this epoch. Our observations also reveal extremely high equivalent-width nebular emission coincident with the luminous AGN jets that is best fit by radiative shocks surrounded by extensive recent star formation. We estimate the total star-formation rate (SFR) could be as high as ∼ 1600 M yr−1 , with the SFR that we attribute to the jet induced burst conservatively 500 M yr−1. The mass-weighted age of the star-formation, tmass < 4 Myr, is consistent with the likely age of the jets responsible for the triggered activity and significantly younger than that measured in the core of the host galaxy. The extreme scale of the potential jet-triggered star-formation activity indicates the potential importance of positive AGN feedback in the earliest stages of massive galaxy formation, with our observations also illustrating the extraordinary prospects for detailed studies of high-redshift galaxies with JWST.KJD acknowledges funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 892117 (HIZRAD) and support from the STFC through an Ernest Rutherford Fellowship (grant number ST/W003120/1). RAW, SHC, and RAJ acknowledge support from NASA JWST Interdisciplinary Scientist grants NAG5-12460, NNX14AN10G, and 80NSSC18K0200 from GSFC. Work by CJC acknowledges support from the European Research Council (ERC) Advanced Investigator Grant EPOCHS (788113). BLF thanks the Berkeley Center for Theoretical Physics for their hospitality during the writing of this paper. MAM acknowledges the support of a National Research Council of Canada Plaskett Fellowship, and the Australian Research Council center of Excellence for All Sky Astrophysics in 3 Dimensions (ASTRO 3D), through project number CE17010001. CNAW acknowledges funding from the JWST/NIRCam contract NASS-0215 to the University of Arizona. TAH is supported by an appointment to the NASA Postdoctoral Program (NPP) at NASA Goddard Space Flight Center, administered by Oak Ridge Associated Universities under contract with NASA.Peer reviewe

PEARLS: Near Infrared Photometry in the JWST North Ecliptic Pole Time Domain Field

We present Near-Infrared (NIR) ground-based Y, J, H, and K imaging obtained in the James Webb Space Telescope North Ecliptic Pole Time Domain Field (TDF) using the MMT-Magellan Infrared Imager and Spectrometer (MMIRS) on the MMT.These new observations cover a field of approximately 230 arcmin^2 in Y, H, and K and 313 arcmin^2 in J. Using Monte Carlo simulations we estimate a 1 sigma depth relative to the background sky of (Y, J, H, K}) = (23.80, 23.53, 23.13, 23.28) in AB magnitudes for point sources at a 95% completeness level. These observations are part of the ground-based effort to characterize this region of the sky, supplementing space-based data obtained with Chandra, NuSTAR, XMM, AstroSat, HST, and JWST. This paper describes the observations and reduction of the NIR imaging and combines these NIR data with archival imaging in the visible, obtained with the Subaru Hyper-Suprime-Cam, to produce a merged catalog of 57,501 sources. The new observations reported here, plus the corresponding multi-wavelength catalog, will provide a baseline for time-domain studies of bright sources in the TDF.Comment: 23 pages, 10 figures. Accepted for publication in ApJS. Images and catalogs available at https://doi.org/10.5281/zenodo.7934393. Data description available under ancillary files and at the Zenodo site. Added a reference, fixed typos in metadat

PEARLS: Near-infrared Photometry in the JWST North Ecliptic Pole Time Domain Field * * Partly based on observations taken with the MMT, a joint facility operated by the University of Arizona and the Smithsonian Institution.

We present near-infrared (NIR) ground-based Y, J, H, and K imaging obtained in the James Webb Space Telescope (JWST) North Ecliptic Pole Time Domain Field (NEP TDF) using the MMT-Magellan Infrared Imager and Spectrometer on the MMT. These new observations cover a field of approximately 230 arcmin2 in Y, H, and K, and 313 arcmin2 in J. Using Monte Carlo simulations, we estimate a 1σ depth relative to the background sky of (Y, J, H, K) = (23.80, 23.53, 23.13, 23.28) in AB magnitudes for point sources at a 95% completeness level. These observations are part of the ground-based effort to characterize this region of the sky, supplementing space-based data obtained with Chandra, NuSTAR, XMM, AstroSat, Hubble Space Telescope, and JWST. This paper describes the observations and reduction of the NIR imaging and combines these NIR data with archival imaging in the visible, obtained with the Subaru Hyper-Suprime-Cam, to produce a merged catalog of 57,501 sources. The new observations reported here, plus the corresponding multiwavelength catalog, will provide a baseline for time-domain studies of bright sources in the NEP TDF

JWST's PEARLS: Mothra, a new kaiju star at z=2.091 extremely magnified by MACS0416, and implications for dark matter models

We report the discovery of Mothra, an extremely magnified monster star, likely a binary system of two supergiant stars, in one of the strongly lensed galaxies behind the galaxy cluster MACS0416. The star is in a galaxy with spectroscopic redshift $z=2.091$ in a portion of the galaxy that is parsecs away from the cluster caustic. The binary star is observed only on the side of the critical curve with negative parity but has been detectable for at least eight years, implying the presence of a small lensing perturber. Microlenses alone cannot explain the earlier observations of this object made with the Hubble Space Telescope. A larger perturber with a mass of at least $10^4$\,\Msun\ offers a more satisfactory explanation. Based on the lack of perturbation on other nearby sources in the same arc, the maximum mass of the perturber is $M< 2.5\times10^6$\,\Msun, making it the smallest substructure constrained by lensing above redshift 0.3. The existence of this millilens is fully consistent with the expectations from the standard cold dark matter model. On the other hand, the existence of such small substructure in a cluster environment has implications for other dark matter models. In particular, warm dark matter models with particle masses below 8.7\,keV are excluded by our observations. Similarly, axion dark matter models are consistent with the observations only if the axion mass is in the range $0.5\times10^{-22}\, {\rm eV} < m_a < 5\times10^{-22}\, {\rm eV}$.Comment: 26 pages and 27 figure