Origin of the Strong Sodium Absorption of the Lensed Supernova 2016geu at z = 0.4

The origin of strong sodium absorption, which has been observed for a few nearby Type Ia supernovae (SNe Ia), remains elusive. Here we analyze two high-signal-to-noise, intermediate-resolution Very Large Telescope/X-shooter spectra at epochs +18 and +27 days past peak brightness of the strongly lensed and multiply imaged Type Ia SN 2016geu, which exploded at a redshift of z = 0.4. We show that SN 2016geu exhibits very strong multiple Na i and Ca ii absorption lines with a large total Na i D rest-frame equivalent width (EW) of 5.2 ± 0.2 Å, among the highest ever detected for an SN Ia and similar to only a handful of nearby SNe Ia with extraordinarily large Na i D EWs. The absorption system is time-invariant and extends over a large velocity span ∼250 km s−1. The majority of the absorption is blueshifted relative to the strongest component, while there are both blueshifted and redshifted components relative to the systemic redshift of the galaxy. The column density ratios and widths of the absorption lines indicate that the absorption likely arises from a combination of interstellar dusty molecular clouds and circumgalactic in- and outflowing material rather than circumstellar matter around the supernova

LensWatch: I. Resolved HST Observations and Constraints on the Strongly-Lensed Type Ia Supernova 2022qmx ("SN Zwicky")

Supernovae (SNe) that have been multiply-imaged by gravitational lensing are rare and powerful probes for cosmology. Each detection is an opportunity to develop the critical tools and methodologies needed as the sample of lensed SNe increases by orders of magnitude with the upcoming Vera C. Rubin Observatory and Nancy Grace Roman Space Telescope. The latest such discovery is of the quadruply-imaged Type Ia SN 2022qmx (aka, "SN Zwicky"; Goobar et al. 2022) at z = 0.3544. SN Zwicky was discovered by the Zwicky Transient Facility (ZTF) in spatially unresolved data. Here we present follow-up Hubble Space Telescope observations of SN Zwicky, the first from the multi-cycle "LensWatch" program (www.lenswatch.org). We measure photometry for each of the four images of SN Zwicky, which are resolved in three WFC3/UVIS filters (F475W, F625W, F814W) but unresolved with WFC3/IR F160W, and produce an analysis of the lensing system using a variety of independent lens modeling methods. We find consistency between time delays estimated with the single epoch of HST photometry and the lens model predictions constrained through the multiple image positions, with both inferring time delays of <1 day. Our lens models converge to an Einstein radius of (0.168+0.009-0.005)", the smallest yet seen in a lensed SN. The "standard candle" nature of SN Zwicky provides magnification estimates independent of the lens modeling that are brighter by ~1.5 mag and ~0.8 mag for two of the four images, suggesting significant microlensing and/or additional substructure beyond the flexibility of our image-position mass models

Adjuvant breast cancer chemotherapy during late-trimester pregnancy: not quite a standard of care

<p>Abstract</p> <p>Background</p> <p>Diagnosis of breast cancer during pregnancy was formerly considered an indication for abortion. The pendulum has since swung to the other extreme, with most reviews now rejecting termination while endorsing immediate anthracycline-based therapy for any pregnant patient beyond the first trimester. To assess the evidence for this radical change in thinking, a review of relevant studies in the fields of breast cancer chemotherapy, pregnancy, and drug safety was conducted.</p> <p>Discussion</p> <p>Accumulating evidence for the short-term safety of anthracycline-based chemotherapy during late-trimester pregnancy represents a clear advance over the traditional norm of therapeutic abortion. Nonetheless, the emerging orthodoxy favoring routine chemotherapy during gestation should continue to be questioned on several grounds: (1) the assumed difference in maternal survival accruing from chemotherapy administered earlier – i.e., during pregnancy, rather than after delivery – has not been quantified; (2) the added survival benefit of adjuvant cytotoxic therapy prescribed within the hormone-rich milieu of pregnancy remains presumptive, particularly for ER-positive disease; (3) the maternal survival benefit associated with modified adjuvant regimens (e.g., weekly schedules, omission of taxanes, etc.) has not been proven equivalent to standard (e.g., post-delivery) regimens; and (4) the long-term transplacental and transgenerational hazards of late-trimester chemotherapy are unknown.</p> <p>Summary</p> <p>Although an incrementally increased risk of cancer-specific mortality is impossible to exclude, mothers who place a high priority on the lifelong well-being of their progeny may be informed that deferring optimal chemotherapy until after delivery is still an option to consider, especially in ER-positive, node-negative and/or last-trimester disease.</p

Preservation of quality of life in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer treated with tucatinib or placebo when added to trastuzumab and capecitabine (HER2CLIMB trial)

AIMS: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer. We evaluated the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB. METHODS: Patients were randomised 2:1 to tucatinib or placebo combined with trastuzumab and capecitabine. Starting with protocol version 7, the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire and EQ visual analogue scale (VAS) were administered at day 1 of cycle 1, every two cycles during cycles 3–9, every three cycles during cycle 12 and thereafter and at each patient's 30-day follow-up visit. RESULTS: Among 364 patients eligible for HR-QoL assessment, 331 (91%) completed ≥1 assessment. EQ-VAS scores were similar for both arms at baseline and maintained throughout treatment. EQ-5D-5L scores were similar between the treatment arms, stable throughout therapy and worsened after discontinuing treatment. Risk of meaningful deterioration (≥7 points) on EQ-VAS was reduced 19% in the tucatinib vs. placebo arm (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.55, 1.18); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.8 months (4.3, -) in the placebo arm. Among patients with brain metastases (n = 164), risk of meaningful deterioration on EQ-VAS was reduced 49% in the tucatinib arm (HR: 0.51; 95% CI: 0.28, 0.93); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.5 months (4.2, -) in the placebo arm. CONCLUSIONS: HR-QoL was preserved for patients with HER2+ metastatic breast cancer who were treated with tucatinib added to trastuzumab and capecitabine and maintained longer with tucatinib therapy than without it among those with brain metastases

Environmental Risk Assessment of Fluctuating Diazinon Concentrations in an Urban and Agricultural Catchment Using Toxicokinetic–Toxicodynamic Modeling

Temporally resolved environmental risk assessment of fluctuating concentrations of micropollutants is presented. We separated the prediction of toxicity over time from the extrapolation from one to many species and from acute to sublethal effects. A toxicokinetic–toxicodynamic (TKTD) model predicted toxicity caused by fluctuating concentrations of diazinon, measured by time-resolved sampling over 108 days from three locations in a stream network, representing urban, agricultural and mixed land use. We calculated extrapolation factors to quantify variation in toxicity among species and effect types based on available toxicity data, while correcting for different test durations with the TKTD model. Sampling from the distribution of extrapolation factors and prediction of time-resolved toxicity with the TKTD model facilitated subsequent calculation of the risk of undesired toxic events. Approximately one-fifth of aquatic organisms were at risk and fluctuating concentrations were more toxic than their averages. Contribution of urban and agricultural sources of diazinon to the overall risk varied. Thus using fixed concentrations as water quality criteria appears overly simplistic because it ignores the temporal dimension of toxicity. However, the improved prediction of toxicity for fluctuating concentrations may be small compared to uncertainty due to limited diversity of toxicity data to base the extrapolation factors on

Methanotrophy, Methylotrophy, the Human Body and Disease

Methylotrophic Bacteria use one-carbon (C1) compounds as their carbon source. They have been known to be associated to the human body for almost 20 years as part of the normal flora and were identified as pathogens in the early 1990s in end-stage HIV patients and chemotherapy patients. In this chapter, I look at C1 compounds in the human body and exposure from the environment and then consider Methylobacterium spp. and Methylorubrum spp. in terms of infections, its role in breast and bowel cancers; Methylococcus capsulatus and its role in inflammatory bowel disease, and Brevibacterium casei and Hyphomicrobium sulfonivorans as part of the normal human flora. I also consider the abundance of methylotrophs from the Actinobacteria being identified in human studies and the potential bias of the ionic strength of culture media and the needs for future work. Within the scope of future work, I consider the need for the urgent assessment of the pathogenic, oncogenic, mutagenic and teratogenic potential of Methylobacterium spp. and Methylorubrum spp. and the need to handle them at higher containment levels until more data are available

Variability in chemotherapy delivery for elderly women with advanced stage ovarian cancer and its impact on survival

Given the survival benefits of adjuvant chemotherapy for advanced ovarian cancer (OC), we examined the associations of survival with the time interval from debulking surgery to initiation of chemotherapy and with the duration of chemotherapy. Among patients ⩾65 years with stages III/IV OC diagnosed between 1991 and 2002 in the Surveillance, Epidemiology, and End Results-Medicare database, we developed regression models of predictors of the time interval from surgery to initiation of chemotherapy and of the total duration of chemotherapy. Survival was examined with Cox proportional hazards models. Among 2558 patients, 1712 (67%) initiated chemotherapy within 6 weeks of debulking surgery, while 846 (33%) began treatment >6 weeks. Older age, black race, being unmarried, and increased comorbidities were associated with delayed initiation of chemotherapy. Delay of chemotherapy was associated with an increase in mortality (hazard ratio (HR)=1.11; 95% CI, 1.0–1.2). Among 1932 patients in the duration of treatment analysis, the 1218 (63%) treated for 3–7 months had better survival than the 714 (37%) treated for ⩽3 months (HR=0.84; 95% CI, 0.75–0.94). This analysis represents one of the few studies describing treatment delivery and outcome in women with advanced OC. Delayed initiation and early discontinuation of chemotherapy were common and associated with increased mortality

Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors

Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. METHODS: The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country. RESULTS: There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P = 4 × 10- 4 and P = 0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54 ± 0.97 mmol/L) than those with the E3 (5.98 ± 1.05 mmol/L) (P = 0.001) and E4 (6.09 ± 1.06 mmol/L) (P = 2 × 10- 4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P = 2 × 10- 6 and P = 3 × 10- 4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (P = 4 × 10- 4 and P = 0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction on lipid outcomes. CONCLUSION: In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts

Measurement of dσ/dyd\sigma/dy of Drell-Yan e+e−e^+e^- pairs in the ZZ Mass Region from ppˉp\bar{p} Collisions at s=1.96\sqrt{s}=1.96 TeV

Submitted to Phys. Letter BWe report on a CDF measurement of the total cross section and rapidity distribution, $d\sigma/dy$, for $q\bar{q}\to \gamma^{*}/Z\to e^{+}e^{-}$ events in the $Z$ boson mass region ($66M_{ee}We report on a CDF measurement of the total cross section and rapidity distribution, dσ/dy, for γ*/Z→e+e− events in the Z boson mass region (66<Mee<116 GeV/c2) produced in p pbar collisions at \sqrt{s}=1.96 TeV with 2.1 fb−1 of integrated luminosity. The measured cross section of 257±16 pb and dσ/dy distribution are compared with Next-to-Leading-Order (NLO) and Next-to-Next-to-Leading-Order (NNLO) QCD theory predictions with CTEQ and MRST/MSTW parton distribution functions (PDFs). There is good agreement between the experimental total cross section and dσ/dy measurements with theoretical calculations with the most recent NNLO PDFs.Peer reviewe