The Abundance of Interstellar Fluorine and Its Implications

We report results from a survey of neutral fluorine (F I) in the interstellar medium. Data from the Far Ultraviolet Spectroscopic Explorer (FUSE) were used to analyze 26 lines of sight lying both in the galactic disk and halo, including lines to Wolf-Rayet stars and through known supernova remnants. The equivalent widths of fluorine resonance lines at 951.871 A and 954.827 A were measured or assigned upper limits and combined with a nitrogen curve of growth to obtain F I column densities. These column densities were then used to calculate fluorine depletions. Comparisons are made to the previous study of F I by Federman et al. (2005) and implications for F I formation and depletion are discussed.Comment: 32 pages, 10 figures, Accepted to Ap

Optical spectrum of proflavine and its ions

Motivated by possible astrophysical and biological applications we calculate visible and near UV spectral lines of proflavine (C13H11N3, 3,6-diaminoacridine) in vacuum, as well as its anion, cation, and dication. The pseudopotential density functional and time-dependent density functional methods are used. We find a good agreement in spectral line positions calculated by two real-time propagation methods and the Lanczos chain method. Spectra of proflavine and its ions show characteristic UV lines which are good candidates for a detection of these molecules in interstellar space and various biological processes

A New FUSE Survey of Interstellar HD

We have used archival FUSE data to complete a survey of interstellar HD in 41 lines of sight with a wide range of extinctions. This follow up to an earlier survey was made to further assess the utility of HD as a cosmological probe; to analyze the HD formation process; and to see what trends with other interstellar properties were present in the data. We employed the curve-of-growth method, supported by line profile fitting, to derive accurate column densities of HD. We find that the N(HD)/2N(H2) ratio is substantially lower than the atomic D/H ratio and conclude that the molecular ratio has no bearing on cosmology, because local processes are responsible for the formation of HD. Based on correlations with E(B-V), H2, CO, and iron depletion, we find that HD is formed in the densest portion of the clouds; the slope of the logN(HD)/log(H2) correlation is greater than 1.0, caused by the destruction rate of HD declining more slowly than that of H2; and, as a sidelight, that the depletions are density dependent.Comment: 30 pages, 13 figures; Accepted for publication in Ap

A High Signal-to-Noise Ratio Composite Spectrum of Gamma-ray Burst Afterglows

We present a composite spectrum of 60 long duration gamma-ray burst (GRB) afterglows with redshifts in the range 0.35<z<6.7 observed with low resolution optical spectra. The composite spectrum covers the wavelength range 700-6600 A in the rest frame and has a mean signal-to-noise ratio of 150 per 1 A pixel and reaches a maximum of ~300 in the range 2500-3500 A. Equivalent widths are measured from metal absorption lines from the Lya line to ~5200 A, and associated metal and hydrogen lines are identified between the Lyman break and Lya line. The average transmission within the Lyman forest is consistent with that found along quasar lines of sight. We find a temporal variation in fine structure lines when dividing the sample into bursts observed within 2 hours from their trigger and those observed later. Other lines in the predominantly neutral gas show variations too, but this is most likely a random effect caused by weighting of individual strong absorption lines and which mimics a temporal variation. Bursts characterized with high or low prompt GRB energy release produce afterglows with similar absorption line strengths, and likewise for bursts with bright or faint optical afterglows. Bursts defined as dark from their optical to X-ray spectral index have stronger absorption lines relative to the optically bright bursts. The composite spectrum has strong CaII and MgII absorption lines as commonly found in dusty galaxies, however, we find no evidence for dust or a significant molecular content based on the non-detection of diffuse interstellar bands. Compared to starburst galaxy spectra, the GRB composite has much stronger fine structure lines, while metal absorption lines are weaker.Comment: Accepted for publication in ApJ, 24 page

High incidence of Noonan syndrome features including short stature and pulmonic stenosis in patients carrying NF1 missense mutations affecting p.Arg1809: genotype-phenotype correlation

Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple cafe-au-lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan-like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P<0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients

The Physics of the B Factories

This work is on the Physics of the B Factories. Part A of this book contains a brief description of the SLAC and KEK B Factories as well as their detectors, BaBar and Belle, and data taking related issues. Part B discusses tools and methods used by the experiments in order to obtain results. The results themselves can be found in Part C

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years