Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH

CUBES : the Cassegrain U-band Efficient Spectrograph

In the era of Extremely Large Telescopes, the current generation of 8-10m facilities are likely to remain competitive at ground-UV wavelengths for the foreseeable future. The Cassegrain U-Band Efficient Spectrograph (CUBES) has been designed to provide high-efficiency (> 40%) observations in the near UV (305-400 nm requirement, 300-420 nm goal) at a spectral resolving power of R >20, 000 (with a lower-resolution, sky-limited mode of R ~7, 000). With the design focusing on maximizing the instrument throughput (ensuring a Signal to Noise Ratio (SNR) ~20 per high-resolution element at 313 nm for U ~18.5 mag objects in 1h of observations), it will offer new possibilities in many fields of astrophysics, providing access to key lines of stellar spectra: a tremendous diversity of iron-peak and heavy elements, lighter elements (in particular Beryllium) and light-element molecules (CO, CN, OH), as well as Balmer lines and the Balmer jump (particularly important for young stellar objects). The UV range is also critical in extragalactic studies: the circumgalactic medium of distant galaxies, the contribution of different types of sources to the cosmic UV background, the measurement of H2 and primordial Deuterium in a regime of relatively transparent intergalactic medium, and follow-up of explosive transients. The CUBES project completed a Phase A conceptual design in June 2021 and has now entered the detailed design and construction phase. First science operations are planned for 2028

Takotsubo Cardiomyopathy in an Elderly Woman with Alzheimer's Disease: A Rare Association. Case Report and Mini-Review of the Literature

NO ABSTRAC

The CUBES science case

International audienceWe introduce the scientific motivations for the development of the Cassegrain U-Band Efficient Spectrograph (CUBES) that is now in construction for the Very Large Telescope. The assembled cases span a broad range of contemporary topics across Solar System, Galactic and extragalactic astronomy, where observations are limited by the performance of current ground-based spectrographs shortwards of 400 nm. A brief background to each case is presented and specific technical requirements on the instrument design that flow-down from each case are identified. These were used as inputs to the CUBES design, that will provide a factor of ten gain in efficiency for astronomical spectroscopy over 300-405 nm, at resolving powers of R ∼ 24,000 and ∼7,000. We include performance estimates that demonstrate the ability of CUBES to observe sources that are up to three magnitudes fainter than currently possible at ground-ultraviolet wavelengths, and we place its predicted performance in the context of existing facillities

CUBES, the Cassegrain U-Band Efficient Spectrograph

In the era of Extremely Large Telescopes, the current generation of 8-10m facilities are likely to remain competitive at ground-UV wavelengths for the foreseeable future. The Cassegrain U-Band Efficient Spectrograph (CUBES) has been designed to provide high-efficiency (>40%) observations in the near UV (305-400 nm requirement, 300-420 nm goal) at a spectral resolving power of R>20,000 (with a lower-resolution, sky-limited mode of R ~ 7,000). With the design focusing on maximizing the instrument throughput (ensuring a Signal to Noise Ratio (SNR) ~20 per high-resolution element at 313 nm for U ~18.5 mag objects in 1h of observations), it will offer new possibilities in many fields of astrophysics, providing access to key lines of stellar spectra: a tremendous diversity of iron-peak and heavy elements, lighter elements (in particular Beryllium) and light-element molecules (CO, CN, OH), as well as Balmer lines and the Balmer jump (particularly important for young stellar objects). The UV range is also critical in extragalactic studies: the circumgalactic medium of distant galaxies, the contribution of different types of sources to the cosmic UV background, the measurement of H2 and primordial Deuterium in a regime of relatively transparent intergalactic medium, and follow-up of explosive transients. The CUBES project completed a Phase A conceptual design in June 2021 and has now entered the detailed design and construction phase. First science operations are planned for 2028