From Molecular Cores to Planet-forming Disks with SIRTF

The SIRTF mission and the Legacy programs will provide coherent data bases for extra-galactic and Galactic science that will rapidly become available to researchers through a public archive. The capabilities of SIRTF and the six legacy programs are described briefly. Then the cores to disks (c2d) program is described in more detail. The c2d program will use all three SIRTF instruments (IRAC, MIPS, and IRS) to observe sources from molecular cores to protoplanetary disks, with a wide range of cloud masses, stellar masses, and star-forming environments. The SIRTF data will stimulate many follow-up studies, both with SIRTF and with other instruments.Comment: 6 pages, from Fourth Cologne-Bonn-Zermatt-Symposium, The Dense Interstellar Matter in Galaxie

Widespread star formation inside galactic outflows

Several models have predicted that stars could form inside galactic outflows and that this would be a new major mode of galaxy evolution. Observations of galactic outflows have revealed that they host large amounts of dense and clumpy molecular gas, which provide conditions suitable for star formation. We have investigated the properties of the outflows in a large sample of galaxies by exploiting the integral field spectroscopic data of the large MaNGA-SDSS4 galaxy survey. We find that star formation occurs inside at least half of the galactic outflows in our sample. We also show that even if star formation is prominent inside many other galactic outflows, this may have not been revealed as the diagnostics are easily dominated by the presence of even faint AGN and shocks. If very massive outflows typical of distant galaxies and quasars follow the same scaling relations observed locally, then the star formation inside high-z outflows can be up to several 100 Msun/yr and could contribute substantially to the early formation of the spheroidal component of galaxies. Star formation in outflows can also potentially contribute to establishing the scaling relations between black holes and their host spheroids. Moreover, supernovae exploding on large orbits can chemically enrich in-situ and heat the circumgalactic and intergalactic medium. Finally, young stars ejected on large orbits may also contribute to the reionization of the Universe

Chains of large gaps between primes

Let $p_n$ denote the $n$-th prime, and for any $k \geq 1$ and sufficiently large $X$, define the quantity $$G_k(X) := \max_{p_{n+k} \leq X} \min( p_{n+1}-p_n, \dots, p_{n+k}-p_{n+k-1} ),$$ which measures the occurrence of chains of $k$ consecutive large gaps of primes. Recently, with Green and Konyagin, the authors showed that $$G_1(X) \gg \frac{\log X \log \log X\log\log\log\log X}{\log \log \log X}$$ for sufficiently large $X$. In this note, we combine the arguments in that paper with the Maier matrix method to show that $$G_k(X) \gg \frac{1}{k^2} \frac{\log X \log \log X\log\log\log\log X}{\log \log \log X}$$ for any fixed $k$ and sufficiently large $X$. The implied constant is effective and independent of $k$.Comment: 16 pages, no figure

The Prostate Health Index adds predictive value to multi-parametric MRI in detecting significant prostate cancers in a repeat biopsy population

Both multi-parametric MRI (mpMRI) and the Prostate Health Index (PHI) have shown promise in predicting a positive biopsy in men with suspected prostate cancer. Here we investigated the value of combining both tests in men requiring a repeat biopsy. PHI scores were measured in men undergoing re-biopsy with an mpMRI image-guided transperineal approach (n = 279, 94 with negative mpMRIs). The PHI was assessed for ability to add value to mpMRI in predicting all or only significant cancers (Gleason ≥7). In this study adding PHI to mpMRI improved overall and significant cancer prediction (AUC 0.71 and 0.75) compared to mpMRI + PSA alone (AUC 0.64 and 0.69 respectively). At a threshold of ≥35, PHI + mpMRI demonstrated a NPV of 0.97 for excluding significant tumours. In mpMRI negative men, the PHI again improved prediction of significant cancers; AUC 0.76 vs 0.63 (mpMRI + PSA). Using a PHI≥35, only 1/21 significant cancers was missed and 31/73 (42%) men potentially spared a re-biopsy (NPV of 0.97, sensitivity 0.95). Decision curve analysis demonstrated clinically relevant utility of the PHI across threshold probabilities of 5-30%. In summary, the PHI adds predictive performance to image-guided detection of clinically significant cancers and has particular value in determining re-biopsy need in men with a negative mpMRI

The longitudinal effect of ejaculation on seminal vesicle fluid volume and whole-prostate ADC as measured on prostate MRI.

OBJECTIVE: To prospectively investigate the longitudinal effect of ejaculatory abstinence on MRI-measured seminal vesicle (SV) volume and whole-prostate ADC over consecutive days. METHODS: 15 healthy male volunteers (mean 35.9 years, range 27-53) underwent 3-T MRI at baseline and 1, 2 and 3 days post-ejaculation. Prostate and SV volumes were derived by volume segmentation and whole-gland apparent diffusion coefficient (ADC) values calculated. A mixed-effects linear regression compared ADC values and prostate/seminal vesicle volumes in each volunteer between studies in a pairwise manner. RESULTS: All subjects completed the four MRIs. Mean prostate volume was 22.45 cm³ (range 13.04-31.21 cm³), with no change between the four studies (p = 0.89-0.99). 13/15 subjects showed SV volume reduction from baseline to day 1, with group-mean decreasing from 6.45 to 4.80 cm³ (-25.6%, p < 0.001), and a significant reduction from baseline to day 2 (-18.1%, p = 0.002). There was a significant volume increase from both day 1 (+21.3%, p = 0.006) and day 2 (+10.2%, p = 0.022) to day 3 post-ejaculation. There was a significant reduction in ADC from 1.105 at baseline to 1.056 × 10¯³ mm²/s at day 1 (mean -4.3%, p = 0.009). CONCLUSION: The longitudinal effect of ejaculation on SV volume was demonstrated. Significant reductions in SV volume and whole-gland ADC were observed post-ejaculation, supporting a 3-day period of abstinence before prostate MRI. KEY POINTS: • Seminal vesicle volume significantly reduced 24 h post-ejaculation remaining reduced at day 2 • Seminal vesicle fluid volume significantly increased from day 1 to day 3 post-ejaculation • There was a significant reduction in whole-gland prostate ADC values day 1 post-ejaculation • 3-day abstinence from ejaculation is required to ensure maximal seminal vesicle distension.The authors acknowledge grant support from the Royal College of Radiologists UK and research support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre

Does a 'direct' transfer protocol reduce time to coronary angiography for patients with non-ST-elevation acute coronary syndromes? A prospective observational study.

OBJECTIVE: National guidelines recommend 'early' coronary angiography within 96 h of presentation for patients with non-ST elevation acute coronary syndromes (NSTE-ACS). Most patients with NSTE-ACS present to their district general hospital (DGH), and await transfer to the regional cardiac centre for angiography. This care model has inherent time delays, and delivery of timely angiography is problematic. The objective of this study was to assess a novel clinical care pathway for the management of NSTE-ACS, known locally as the Heart Attack Centre-Extension or HAC-X, designed to rapidly identify patients with NSTE-ACS while in DGH emergency departments (ED) and facilitate transfer to the regional interventional centre for 'early' coronary angiography. METHODS: This was an observational study of 702 patients divided into two groups; 391 patients treated before the instigation of the HAC-X pathway (Pre-HAC-X), and 311 patients treated via the novel pathway (Post-HAC-X). Our primary study end point was time from ED admission to coronary angiography. We also assessed the length of hospital stay. RESULTS: Median time from ED admission to coronary angiography was 7.2 (IQR 5.1-10.2) days pre-HAC-X compared to 1.0 (IQR 0.7-2.0) day post-HAC-X (p<0.001). Median length of hospital stay was 3.0 (IQR 2.0-6.0) days post-HAC-X v 9.0 (IQR 6.0-14.0) days pre-HAC-X (p<0.0005). This equates to a reduction of six hospital bed days per NSTE-ACS admission. CONCLUSIONS: The introduction of this novel care pathway was associated with significant reductions in time to angiography and in total hospital bed occupancy for patients with NSTE-ACS

Stabilization of angiotensin-(1-7) by key substitution with a cyclic non-natural amino acid

Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin-aldosterone system (RAAS), is a promising candidate as a treatment for cancer that reflects its antiproliferative and anti-angiogenic properties. However, the peptide’s therapeutic potential is limited by the short half-life and low bioavailability resulting from rapid enzymatic metabolism by peptidases including angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report the facile assembly of three novel Ang-(1-7) analogues by solid-phase peptide synthesis which incorporates the cyclic non-natural δ-amino acid ACCA. The analogues containing the ACCA substitution at the site of ACE cleavage exhibit complete resistance to human ACE, while substitution at the DDP3 cleavage site provided stability against DPP 3 hydrolysis. Furthermore, the analogues retain the anti-proliferative properties of Ang-(1-7) against the 4T1 and HT-1080 cancer cell lines. These results suggest that ACCA-substituted Ang-(1-7) analogues which show resistance against proteolytic degradation by peptidases known to hydrolyze the native heptapeptide may be novel therapeutics in the treatment of cancer

Concentration analysis and cocompactness

Loss of compactness that occurs in may significant PDE settings can be expressed in a well-structured form of profile decomposition for sequences. Profile decompositions are formulated in relation to a triplet $(X,Y,D)$, where $X$ and $Y$ are Banach spaces, $X\hookrightarrow Y$, and $D$ is, typically, a set of surjective isometries on both $X$ and $Y$. A profile decomposition is a representation of a bounded sequence in $X$ as a sum of elementary concentrations of the form $g_kw$, $g_k\in D$, $w\in X$, and a remainder that vanishes in $Y$. A necessary requirement for $Y$ is, therefore, that any sequence in $X$ that develops no $D$-concentrations has a subsequence convergent in the norm of $Y$. An imbedding $X\hookrightarrow Y$ with this property is called $D$-cocompact, a property weaker than, but related to, compactness. We survey known cocompact imbeddings and their role in profile decompositions

Positron emission tomography imaging of coronary atherosclerosis

Inflammation has a central role in the progression of coronary atherosclerosis. Recent developments in cardiovascular imaging with the advent of hybrid positron emission tomography have provided a window into the molecular pathophysiology underlying coronary plaque inflammation. Using novel radiotracers targeted at specific cellular pathways, the potential exists to observe inflammation, apoptosis, cellular hypoxia, microcalcification and angiogenesis in vivo. Several clinical studies are now underway assessing the ability of this hybrid imaging modality to inform about atherosclerotic disease activity and the prediction of future cardiovascular risk. A better understanding of the molecular mechanisms governing coronary atherosclerosis may be the first step toward offering patients a more stratified, personalized approach to treatment