Searching for Failed Supernovae With Astrometric Binaries

Stars in the mass range 8 Msun<M<30 Msun are thought to end their lives as luminous supernovae that leave behind a neutron star. However, if a substantial fraction of these stars instead ended as black-hole remnants, without producing a supernova (a `failed' supernova), how would one know? We show that, under plausible assumptions, the Hipparcos catalog should contain about 30 f_{fail} astrometric binaries with black-hole companions, where f_{fail} is the fraction of supernovae that fail. Since no black-hole astrometric binaries are found in Hipparcos, one might like to conclude that such failed supernovae are very rare. However, the most important assumption required for this argument, the initial companion mass function (ICMF) of G stars (the majority of Hipparcos stars) in the high-mass companion regime, is without any observational basis. We show how the ICMF of G stars can be measured using the Full-Sky Astrometric Explorer (FAME), thereby permitting an accurate measurement of the rate of supernovae that fail.Comment: Submitted to ApJ, 14 pages including 4 figure

Peanut ball for decreasing length of labor: A systematic review and meta-analysis of randomized controlled trials

INTRODUCTION: Prolonged length of labor is associated with increased maternal and neonatal complications. Therefore, great attention has been given to interventions aimed at reducing the length of labor. One such intervention is the peanut ball, a large elongated exercise ball placed between a woman's legs during labor. OBJECTIVE: The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to assess the effect of the use of peanut ball in reducing length of labor. STUDY DESIGN: Data sources: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library were searched from inception until January 2019. SELECTION CRITERIA: Selection criteria included RCTs of laboring women with singleton gestations in cephalic presentation at term (≥37weeks) who were randomized to either use of peanut ball or control group (no peanut ball). DATA COLLECTION AND ANALYSIS: Four trials with 648 nulliparous and multiparous women in spontaneous or induced labor were identified and included. 330 women were randomized to the intervention (peanut ball between the knees during labor) and 318 women to the control. Summary measures were reported as mean difference (MD) with 95% of confidence interval (CI) using the random effects model of DerSimonian and Laird. The primary outcome was total length of labor. PROSPERO Registration Number: CRD42018082438 RESULTS: Total length of labor was 79min shorter in the peanut ball group, but this was not significant (MD -79.1 min, 95% CI -204.9, 46.7). Peanut ball use showed trends toward higher incidence of spontaneous vaginal deliveries (RR 1.1, 95% CI 1.0, 1.2) and lower incidence of cesarean deliveries (RR 0.8, 95% CI 0.6, 1.0). CONCLUSIONS: Peanut ball use was not associated with a significant decrease in total length of labor. Since there were trends toward reductions in length of labor, an increased incidence in spontaneous vaginal deliveries, and lower incidence of cesarean deliveries, more research is needed

Cost-minimisation analysis of a treat-and-extend regimen with anti-VEGFs in patients with neovascular age-related macular degeneration

PURPOSE: Although intraocular anti-vascular endothelial growth factors (anti-VEGFs) are effective as treatment of neovascular age-related macular degeneration (nAMD), the (economic) burden on the healthcare system is considerable. A treat-and-extend (T&E) regimen is associated with a lower number of injections without compromising the effectiveness and can therefore help optimise nAMD treatment. This study investigates the per-patient costs associated with nAMD treatment, when using aflibercept, bevacizumab, or ranibizumab with a T&E regimen. METHODS: In this cost-minimisation model, the per-patient costs in the Netherlands were modelled using a healthcare payers’ perspective over a 3-year time horizon with the assumption that efficacy of treatments is similar. Additionally, the break-even price of the different anti-VEGFs was calculated relative to the cheapest option and injection frequency. RESULTS: The injection frequency varied from 14.2 for aflibercept to 27.4 for bevacizumab in 3 years. Nonetheless, bevacizumab remains the cheapest treatment option (€14,215), followed by aflibercept (€18,202) and ranibizumab (€31,048). The medication covers the majority of the per-patient costs for aflibercept and ranibizumab, while administration covers the majority of the per-patient costs for bevacizumab. The break-even prices of aflibercept and ranibizumab are respectively €507 and €60.58 per injection. Brolucizumab was included in the scenario analysis and was more expensive than aflibercept (€20,446). Brolucizumab should reduce to 13.8 injections over 3 years to be as costly as aflibercept. CONCLUSION: Bevacizumab is the cheapest anti-VEGF treatment. The list prices of all anti-VEGFs should reduce to be as costly as bevacizumab. Aflibercept is the second-choice treatment and so far brolucizumab is not

Chromosomal instability in untreated primary prostate cancer as an indicator of metastatic potential.

BackgroundMetastatic prostate cancer (PC) is highly lethal. The ability to identify primary tumors capable of dissemination is an unmet need in the quest to understand lethal biology and improve patient outcomes. Previous studies have linked chromosomal instability (CIN), which generates aneuploidy following chromosomal missegregation during mitosis, to PC progression. Evidence of CIN includes broad copy number alterations (CNAs) spanning &gt; 300 base pairs of DNA, which may also be measured via RNA expression signatures associated with CNA frequency. Signatures of CIN in metastatic PC, however, have not been interrogated or well defined. We examined a published 70-gene CIN signature (CIN70) in untreated and castration-resistant prostate cancer (CRPC) cohorts from The Cancer Genome Atlas (TCGA) and previously published reports. We also performed transcriptome and CNA analysis in a unique cohort of untreated primary tumors collected from diagnostic prostate needle biopsies (PNBX) of localized (M0) and metastatic (M1) cases to determine if CIN was linked to clinical stage and outcome.MethodsPNBX were collected from 99 patients treated in the VA Greater Los Angeles (GLA-VA) Healthcare System between 2000 and 2016. Total RNA was extracted from high-grade cancer areas in PNBX cores, followed by RNA sequencing and/or copy number analysis using OncoScan. Multivariate logistic regression analyses permitted calculation of odds ratios for CIN status (high versus low) in an expanded GLA-VA PNBX cohort (n = 121).ResultsThe CIN70 signature was significantly enriched in primary tumors and CRPC metastases from M1 PC cases. An intersection of gene signatures comprised of differentially expressed genes (DEGs) generated through comparison of M1 versus M0 PNBX and primary CRPC tumors versus metastases revealed a 157-gene "metastasis" signature that was further distilled to 7-genes (PC-CIN) regulating centrosomes, chromosomal segregation, and mitotic spindle assembly. High PC-CIN scores correlated with CRPC, PC-death and all-cause mortality in the expanded GLA-VA PNBX cohort. Interestingly, approximately 1/3 of M1 PNBX cases exhibited low CIN, illuminating differential pathways of lethal PC progression.ConclusionsMeasuring CIN in PNBX by transcriptome profiling is feasible, and the PC-CIN signature may identify patients with a high risk of lethal progression at the time of diagnosis

Antenatal intervention for congenital fetal lower urinary tract obstruction (LUTO): a systematic review and meta-analysis.

To evaluate the effectiveness of antenatal intervention for the treatment of congenital lower urinary tract obstruction (LUTO) in improving perinatal survival and postnatal renal function. METHODS: Electronic databases were searched from their inception until May 2018. Selection criteria included randomized controlled trials and controlled nonrandomized observational studies including fetuses with ultrasound evidence of LUTO evaluating antenatal intervention for improving perinatal outcomes. Any type of intervention was analyzed. The primary outcome was perinatal survival. The secondary outcome was postnatal survival with normal renal function. The summary measures were reported as summary odds ratio (OR) with 95% of confidence interval (CI). RESULTS: Ten articles with a total of 355 fetuses were included in the meta-analysis. Inclusion criteria of the selected studies were singleton pregnancy with severe LUTO confirmed on detailed fetal ultrasound examination. Nine studies, analyzed the efficacy of vesico-amniotic shunt performed in the second trimester. The overall estimate survival was higher in the vesico-amniotic shunt group compared to the conservative group (OR 2.54, 95% CI 1.14-5.67). 64/112 fetuses (57.1%) survived in the vesico-amniotic shunt group compared to 52/134 (38.8%) in the control group. Five studies reported on postnatal renal function between 6 months and 2 years. Postnatal renal function was higher in the vesico-amniotic shunt group compared to the conservative group (OR 2.09, 95% CI 0.74-5.9). Fetal cystoscopy was performed in only two included studies. Overall, 45 fetuses underwent fetal cystoscopy. The perinatal survival was higher in the cystoscopy group compared to the conservative management group (OR 2.63, 95% CI 1.07-6.47). Normal renal function was noted in 13/34 fetuses in the cystoscopy group versus 12/61 in the conservative management group at 6 months follow-up (OR 1.75, 95% CI 1.05-2.92) Conclusions: Antenatal bladder drainage appears to improve perinatal survival in cases of LUTO. Further randomized trials with long-term follow-up are required to determine the role of antenatal treatment in clinical setting

Crater formation by fast ions: comparison of experiment with Molecular Dynamics simulations

An incident fast ion in the electronic stopping regime produces a track of excitations which can lead to particle ejection and cratering. Molecular Dynamics simulations of the evolution of the deposited energy were used to study the resulting crater morphology as a function of the excitation density in a cylindrical track for large angle of incidence with respect to the surface normal. Surprisingly, the overall behavior is shown to be similar to that seen in the experimental data for crater formation in polymers. However, the simulations give greater insight into the cratering process. The threshold for crater formation occurs when the excitation density approaches the cohesive energy density, and a crater rim is formed at about six times that energy density. The crater length scales roughly as the square root of the electronic stopping power, and the crater width and depth seem to saturate for the largest energy densities considered here. The number of ejected particles, the sputtering yield, is shown to be much smaller than simple estimates based on crater size unless the full crater morphology is considered. Therefore, crater size can not easily be used to estimate the sputtering yield.Comment: LaTeX, 7 pages, 5 EPS figures. For related figures/movies, see: http://dirac.ms.virginia.edu/~emb3t/craters/craters.html New version uploaded 5/16/01, with minor text changes + new figure

Turnover of dimethylsulfoniopropionate and dimethylsulfide in the marine environment:A mesocosm experiment

The production of dimethylsulfoniopropionate (DMSP) by marine phytoplankton and the fate of the produced DMSP and dimethylsulfide (DMS) were studied in 4 pelagic mesocosms during an algal bloom over a period of 1 mo. Bacterial numbers, concentrations of particulate and dissolved DMSP, DMS, and chlorophyll a were monitored, as well as the turnover rates of DMS and DMSP. Of the total amount of DMSP produced, only a fraction could be detected as DMS in the water column. DMS production in the water column did not necessarily correlate with algal senescence, but also occurred during the maximum of the algal bloom. The flux of DMS to the atmosphere played a minor role as a sink for DMS. Evidence is presented that shows bacterial consumption to be a major sink for DMS, under conditions of both high and low DMS water concentrations. DMSP was degraded either via cleavage or via demethylation; the results indicate a predominant role for the latter route

Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p &lt; 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization

Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: a systematic review

Background: Intrahepatic cholestasis of pregnancy (ICP) is characterized by the elevation of total bile acids (TBAs). The primary concern in women with ICP is the increased risk of stillbirth. ICP is generally considered as “mild” when TBA levels range from 10 to 39 µmol/L and “severe” with levels greater than 40 µmol/L, although levels of TBA ≥100 µmol/L have been also considered as a further threshold of severity. Objective: To quantify the association between different severities of ICP (TBA 10–39, 40–99, and ≥100 µmol/L) and perinatal death. Data sources: Medline, Embase, Scopus, Web of Sciences, and ClinicalTrial.gov were searched from the inception of each database to February 2019. Methods of study selection: Randomized, cohort, case-control, or case series studies reporting maternal and perinatal outcomes on women with ICP by the three prespecified TBA levels (10–39, 40–99, and ≥100 µmol/L) were included. We excluded multiple gestations and trials which included an intervention. The analysis was performed with Pearson chi-square and Fisher’s exact test as appropriate. Continuous outcomes were compared using metaregression with inverse variance weighting using reported sample sizes and standard deviations. Pairwise comparisons used a Bonferroni correction to control for multiple testing. Tabulation, integration, and results: Six articles including 1280 singleton pregnancies affected by ICP were included in the systematic review. Out of the 1280 singleton pregnancies affected by ICP included, 118 had ICP with TBA ≥100 µmol/L. Perinatal death was more common in women with TBA ≥100 µmol/L (0.4% for TBA 10-39 μmol/L versus 0.3% for TBA 40-99 μmol/L versus 6.8% for TBA ≥ 100 μmol/L, p <.0001). Of the 8 perinatal deaths in the TBA ≥100 µmol/L group, 3 occurred ≥34 weeks. TBA ≥100 µmol/L increased the risk of spontaneous preterm birth (PTB) (5.4% versus 8.6% versus 18.2% respectively, p <.0001) and iatrogenic PTB (10.8% versus 21.6% versus 35.8% respectively, p<.0001) as well as meconium-stained amniotic fluid (9.0% versus 18.4% versus 31.6% respectively, p <.0001). Conclusions: Maternal TBA ≥100 µmol/L is associated with a 6.8% incidence of perinatal death, most of which (5.9% overall) are stillbirths, while TBA <100 µmol/L are associated with an incidence of perinatal death of 0.3%. It may be reasonable to consider late preterm delivery (at about 35–36 weeks) in women with TBA ≥100 µmol/L

Hepatic Mitochondrial Alteration in CD-1 Mice Associated with Prenatal Exposures to Low Doses of Perfluorooctanoic Acid (PFOA)

Perfluorooctanoic acid (PFOA) is a perfluoroalkyl acid primarily used as an industrial surfactant. It persists in the environment and has been linked to potentially toxic and/or carcinogenic effects in animals and people. As a known activator of peroxisome proliferator-activated receptors (PPARs), PFOA exposure can induce defects in fatty acid oxidation, lipid transport, and inflammation. Here, pregnant CD-1 mice were orally gavaged with 0, 0.01, 0.1, 0.3 and 1 mg/kg of PFOA from gestation days (GD) 1 through 17. On postnatal day (PND) 21, histopathologic changes in the livers of offspring included hepatocellular hypertrophy and periportal inflammation that increased in severity by PND 91 in an apparent dose-dependent response. Transmission electron microscopy (TEM) of selected liver sections from PND 91 mice revealed PFOA-induced cellular damage and mitochondrial abnormalities with no evidence of peroxisome proliferation. Within hypertrophied hepatocytes, mitochondria were not only increased in number, but also exhibited altered morphologies suggestive of increased and/or uncontrolled fission and fusion reactions. These findings suggest that peroxisome proliferation is not a component of PFOA-induced hepatic toxicity in animals that are prenatally exposed to low doses of PFOA