The Top Ten List of Gravitational Lens Candidates from the HST Medium Deep Survey

A total of 10 good candidates for gravitational lensing have been discovered in the WFPC2 images from the HST Medium Deep Survey (MDS) and archival primary observations. These candidate lenses are unique HST discoveries, i.e. they are faint systems with sub-arcsecond separations between the lensing objects and the lensed source images. Most of them are difficult objects for ground-based spectroscopic confirmation or for measurement of the lens and source redshifts. Seven are ``strong lens'' candidates which appear to have multiple images of the source. Three are cases where the single image of the source galaxy has been significantly distorted into an arc. The first two quadruply lensed candidates were reported in Ratnatunga et al 1995 (ApJL, 453, L5) We report on the subsequent eight candidates and describe them with simple models based on the assumption of singular isothermal potentials. Residuals from the simple models for some of the candidates indicate that a more complex model for the potential will probably be required to explain the full structural detail of the observations once they are confirmed to be lenses. We also discuss the effective survey area which was searched for these candidate lens objects.Comment: 26 pages including 12 figures and 10 tables. AJ Vol. 117, No.

New "Einstein Cross" Gravitational Lens Candidates in HST WFPC2 Survey Images

We report the serendipitous discovery of ``Einstein cross'' gravitational lens candidates using the Hubble Space Telescope. We have so far discovered two good examples of such lenses, each in the form of four faint blue images located in a symmetric configuration around a red elliptical galaxy. The high resolution of HST has facilitated the discovery of this optically selected sample of faint lenses with small (~1 arcsec) separations between the (I ~ 25-27) lensed components and the much brighter (I ~ 19-22) lensing galaxies. The sample has been discovered in the routine processing of HST fields through the Medium Deep Survey pipeline, which fits simple galaxy models to broad band filter images of all objects detected in random survey fields using WFPC2. We show that the lens configuration can be modeled using the gravitational field potential of a singular isothermal ellipsoidal mass distribution. With this model the lensing potential is very similar, both in ellipticity and orientation, to the observed light distribution of the elliptical galaxy, as would occur when stars are a tracer population. The model parameters and associated errors have been derived by 2-dimensional analysis of the observed images. The maximum likelihood procedure iteratively converges simultaneously on the model for the lensing elliptical galaxy and the source of the lensed components. A systematic search is in progress for other gravitational lens candidates in the HST Medium Deep Survey. This should eventually lead to a good statistical estimate for lensing probabilities, and enable us to probe the cosmological component of the observed faint blue galaxy population.Comment: Accepted for Astrophysical Journal Letters, 1995 November 1 LaTex, 10 pages, includes 2 figures 1 table, tarred gzip uuencoded using uufiles scrip

No evidence of BRCA2 mutations in chromosome 13q-linked Utah high-risk prostate cancer pedigrees

<p>Abstract</p> <p>Background</p> <p>Germline mutations in the <it>BRCA2 </it>gene have been suggested to account for about 5% of familial prostate cancer; mutations have been reported in 2% of early onset (i.e., ≤ 55 years) prostate cancer cases and a segregating founder mutation has been identified in Iceland (999del5). However, the role of <it>BRCA2 </it>in high risk prostate cancer pedigrees remains unclear.</p> <p>Findings</p> <p>We examined the potential involvement of <it>BRCA2 </it>in a set offive high-risk prostate cancer pedigrees in which all prostate cases were no more distantly related than two meioses from another case, and the resulting cluster contained at least four prostate cancer cases. We selected these five pedigrees from a larger dataset of 59 high-risk prostate cancer pedigrees analyzed in a genome-wide linkage screen. Selected pedigrees showed at least nominal linkage evidence to the <it>BRCA2 </it>region on chromosome 13q. We mutation screened all coding regions and intron/exon boundaries of the <it>BRCA2 </it>gene in the youngest prostate cancer case who carried the linked 13q segregating haplotype, as well as in a distantly related haplotype carrier to confirm any segregation. We observed no known protein truncating <it>BRCA2 </it>deleterious mutations. We identified one non-segregating <it>BRCA2 </it>variant of uncertain significance, one non-segregating intronic variant not previously reported, and a number of polymorphisms.</p> <p>Conclusion</p> <p>In this set of high-risk prostate cancer pedigrees with at least nominal linkage evidence to <it>BRCA2</it>, we saw no evidence for segregating <it>BRCA2 </it>protein truncating mutations in heritable prostate cancer.</p

The morphological mix of field galaxies to I=24.25 magnitudes (b=26 magnitudes) from a deep Hubble Space Telescope WFPC2 image

We determine the morphological mix of field galaxies down to $m_{I}\simeq 24.25$ mag ($m_{B}\sim 26.0$ mag) from a single ultradeep HST WFPC2 image in both the $V_{606}$ and $I_{814}$ filters. In total, we find 227 objects with $m_{I}\le 24.5$ mag and classify these into three types: ellipticals (16%), early-type spirals (37%) and late-type spirals/Irregulars (47%). The differential number counts for each type are compared to simple models in a standard flat cosmology. We find that both the elliptical and early-type spiral number counts are well described by {\it little or no}-evolution models, but only when normalized at $b_{J} = 18.0$ mag. Given the uncertainties in the luminosity function (LF) normalization, both populations are consistent with a mild evolutionary scenario based on a normal/low rate of star-formation. This constrains the end of the last {\it major} star-formation epoch in the giant galaxy populations to $z\geq 0.8$. Conversely, the density of the observed late-type/Irregular population is found to be a factor of 10 in excess of the conventional no-evolution model. This large population might be explained by either a modified {\it local} dwarf-rich LF, and/or strong evolution acting on the {\it local} LF. For the dwarf-rich case, a {\it steep} faint-end Schechter-slope ($\alpha\simeq -1.8$) is required plus a five-fold increase in the dwarf normalization. For a purely evolving model based on a {\it flat} Loveday {\it et al.} (1992) LF ($\alpha\simeq -1.0$), a ubiquitous starburst of $\Delta I\sim$2.0 mag is needed at z$\simeq 0.5$ for the {\it entire} late-type population. We argue for a combination of these possibilities, and show that for a steep Marzke {\it et al.} (1994) LF ($\alpha\simeq -1.5$), a starburst of $\sim$ 1.3 mag is requiredComment: 9 pages, 3 figures (2 colour). The figures are available at http://www.phys.unsw.edu.au/~spd/bib.htm

Comparison against 186 canid whole genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor.

Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic drivers of clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world

Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry

Adult height is a classic polygenic trait of high heritability (h2 ∼0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ∼10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4×10−12 and 2p14-rs4315565, P = 1.2×10−8). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7×10−4 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P<0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes