SN~2012cg: Evidence for Interaction Between a Normal Type Ia Supernova and a Non-Degenerate Binary Companion

We report evidence for excess blue light from the Type Ia supernova SN 2012cg at fifteen and sixteen days before maximum B-band brightness. The emission is consistent with predictions for the impact of the supernova on a non-degenerate binary companion. This is the first evidence for emission from a companion to a SN Ia. Sixteen days before maximum light, the B-V color of SN 2012cg is 0.2 mag bluer than for other normal SN~Ia. At later times, this supernova has a typical SN Ia light curve, with extinction-corrected M_B = -19.62 +/- 0.02 mag and Delta m_{15}(B) = 0.86 +/- 0.02. Our data set is extensive, with photometry in 7 filters from 5 independent sources. Early spectra also show the effects of blue light, and high-velocity features are observed at early times. Near maximum, the spectra are normal with a silicon velocity v_{Si} = -10,500$ km s^{-1}. Comparing the early data with models by Kasen (2010) favors a main-sequence companion of about 6 solar masses. It is possible that many other SN Ia have main-sequence companions that have eluded detection because the emission from the impact is fleeting and faint.Comment: accepted to Ap

The Early Effects of Rapid Androgen Deprivation on Human Prostate Cancer.

The androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa). Therefore, understanding how ARs regulate the human transcriptome is of paramount importance. The early effects of castration on human PCa have not previously been studied 27 patients medically castrated with degarelix 7 d before radical prostatectomy. We used mass spectrometry, immunohistochemistry, and gene expression array (validated by reverse transcription-polymerase chain reaction) to compare resected tumour with matched, controlled, untreated PCa tissue. All patients had levels of serum androgen, with reduced levels of intraprostatic androgen at prostatectomy. We observed differential expression of known androgen-regulated genes (TMPRSS2, KLK3, CAMKK2, FKBP5). We identified 749 genes downregulated and 908 genes upregulated following castration. AR regulation of α-methylacyl-CoA racemase expression and three other genes (FAM129A, RAB27A, and KIAA0101) was confirmed. Upregulation of oestrogen receptor 1 (ESR1) expression was observed in malignant epithelia and was associated with differential expression of ESR1-regulated genes and correlated with proliferation (Ki-67 expression).We thank CRUK, The NIHR, The Academy of Medical Sciences(RG:63397) and the National Cancer Research Prostate Cancer: Mechanisms of Progression and Treatment (ProMPT) collaborative (G0500966/75466), Hutchison Whampoa Limited, the Human Research Tissue Bank (Addenbrooke’s Hospital, supported by the NIHR Cambridge BRC), and Cancer Research UK

Type 2 innate lymphoid cells treat and prevent acute gastrointestinal graft-versus-host disease

Acute graft-versus-host disease (aGVHD) is the most common complication for patients undergoing allogeneic stem cell transplantation. Despite extremely aggressive therapy targeting donor T cells, patients with grade III or greater aGVHD of the lower GI tract, who do not respond to therapy with corticosteroids, have a dismal prognosis. Thus, efforts to improve understanding of the function of local immune and non-immune cells in regulating the inflammatory process in the GI tract during aGVHD are needed. Here, we demonstrate, using murine models of allogeneic BMT, that type 2 innate lymphoid cells (ILC2s) in the lower GI tract are sensitive to conditioning therapy and show very limited ability to repopulate from donor bone marrow. Infusion of donor ILC2s was effective in reducing the lethality of aGVHD and in treating lower GI tract disease. ILC2 infusion was associated with reduced donor proinflammatory Th1 and Th17 cells, accumulation of donor myeloid-derived suppressor cells (MDSCs) mediated by ILC2 production of IL-13, improved GI tract barrier function, and a preserved graft-versus-leukemia (GVL) response. Collectively, these findings suggest that infusion of donor ILC2s to restore gastrointestinal tract homeostasis may improve treatment of severe lower GI tract aGVHD

Quantitative breast density analysis to predict interval and node-positive cancers in pursuit of improved screening protocols: a case-control study.

Funder: Policy Research Unit in Cancer Awareness, Screening and early Diagnosis, PR-PRU-1217-21601Funder: American Cancer Society NHPDCSGBR-GBRLONG Policy Research Unit in Cancer Awareness, Screening and early Diagnosis, PR-PRU-1217-21601BACKGROUND: This study investigates whether quantitative breast density (BD) serves as an imaging biomarker for more intensive breast cancer screening by predicting interval, and node-positive cancers. METHODS: This case-control study of 1204 women aged 47-73 includes 599 cancer cases (302 screen-detected, 297 interval; 239 node-positive, 360 node-negative) and 605 controls. Automated BD software calculated fibroglandular volume (FGV), volumetric breast density (VBD) and density grade (DG). A radiologist assessed BD using a visual analogue scale (VAS) from 0 to 100. Logistic regression and area under the receiver operating characteristic curves (AUC) determined whether BD could predict mode of detection (screen-detected or interval); node-negative cancers; node-positive cancers, and all cancers vs. controls. RESULTS: FGV, VBD, VAS, and DG all discriminated interval cancers (all p < 0.01) from controls. Only FGV-quartile discriminated screen-detected cancers (p < 0.01). Based on AUC, FGV discriminated all cancer types better than VBD or VAS. FGV showed a significantly greater discrimination of interval cancers, AUC = 0.65, than of screen-detected cancers, AUC = 0.61 (p < 0.01) as did VBD (0.63 and 0.53, respectively, p < 0.001). CONCLUSION: FGV, VBD, VAS and DG discriminate interval cancers from controls, reflecting some masking risk. Only FGV discriminates screen-detected cancers perhaps adding a unique component of breast cancer risk

Excellent outcomes of laparoscopic esophagomyotomy for achalasia in patients older than 60 years of age

The effectiveness of an esophagomyotomy for dysphagia in elderly patients with achalasia has been questioned. This study was designed to provide an answer. A total of 162 consecutive patients with achalasia who had a laparoscopic myotomy and Dor fundoplication and who were available for follow-up interview were divided by age: &lt;60 years (range, 14–59; 118 patients), and ≥60 years (range, 60–93; 44 patients). Primary outcome measures were severity of dysphagia, regurgitation, heartburn, and chest pain before and after the operation as assessed on a four-point Likert scale, and the need for postoperative dilatation or revisional surgery. Follow-up averaged 64 months. Older patients had less dysphagia (mean score 3.6 vs. 3.9; P &lt; 0.01) and less chest pain (1.0 vs. 1.8; P &lt; 0.01). Regurgitation (3.0 vs. 3.2; P = not significant (NS)) and heartburn (1.6 vs. 2.0, P = NS) were similar. Older patients were no different in degree of esophageal dilation, manometric findings, number of previous pneumatic dilatations, or previous botulinum toxin therapy. None of the older patients had previously had an esophagomyotomy, whereas 14% of younger patients had (P &lt; 0.01). After laparoscopic myotomy, older patients had better relief of dysphagia (mean score 1.0 vs 1.6; P &lt; 0.01), less heartburn (0.8 vs. 1.1; P = 0.03), and less chest pain (0.2 vs. 0.8, P &lt; 0.01). Complication rates were similar. Older patients did not require more postoperative dilatations (22 patients vs. 10 patients; P = 0.7) or revisional surgery for recurrent or persistent symptoms (3 vs. 1 patients; P = 0.6). Satisfaction scores did not differ, and more than 90% of patients in both groups said in retrospect they would have undergone the procedure if they had known beforehand how it would turn out. This retrospective review with long follow-up supports laparoscopic esophagomyotomy as first-line therapy in older patients with achalasia. They appeared to benefit even more than younger patients

A mouse informatics platform for phenotypic and translational discovery

The International Mouse Phenotyping Consortium (IMPC) is providing the world’s first functional catalogue of a mammalian genome by characterising a knockout mouse strain for every gene. A robust and highly structured informatics platform has been developed to systematically collate, analyse and disseminate the data produced by the IMPC. As the first phase of the project, in which 5000 new knockout strains are being broadly phenotyped, nears completion, the informatics platform is extending and adapting to support the increasing volume and complexity of the data produced as well as addressing a large volume of users and emerging user groups. An intuitive interface helps researchers explore IMPC data by giving overviews and the ability to find and visualise data that support a phenotype assertion. Dedicated disease pages allow researchers to find new mouse models of human diseases, and novel viewers provide high-resolution images of embryonic and adult dysmorphologies. With each monthly release, the informatics platform will continue to evolve to support the increased data volume and to maintain its position as the primary route of access to IMPC data and as an invaluable resource for clinical and non-clinical researchers