Infiltrating T-cell markers in cervical carcinogenesis: a systematic review and meta-analysis.

Funder: Intramural Research Program of the National Cancer Institute at the National Institutes of Health (Z01 CP010124-21).BACKGROUND: The host adaptive immune response helps determine which cervical HPV infections persist and progress to precancer and cancer, and systematic characterisation of T-cell infiltration would help inform key steps in cervical carcinogenesis. METHODS: A systematic review and meta-analysis were conducted of infiltrating T-cells in normal cervix, low-grade lesions, high-grade lesions, and invasive cancers including epithelial, stromal, and total tissue and the following markers: CD3, CD4, CD8, FoxP3, CD25, and the CD4:CD8 ratio. An additional qualitative review summarised longitudinal data on associations between infiltrating T-cells and cervical disease persistence, regression, progression, or prognosis. RESULTS: There were fewer CD3+, CD4+, and CD8+ cells in cervical lesions and more cells in cancers compared to normal epithelium. FoxP3 and CD25+ regulatory T-cell infiltration is high in persistent and precancerous lesions, and longitudinal data show improved outcomes with lower regulatory T-cell levels. CONCLUSIONS: Successful immune evasion may reduce T-cell infiltration in HPV infected and precancerous epithelium, while invasive cancers are highly immunogenic, and regulatory T-cell infiltration increases with cervical disease progression. Understanding these factors may have prognostic value and could aid in novel treatment development and clinical guidelines, but published data are highly heterogeneous and leave important gaps to be filled by future studies

PS1-10afx at z = 1.388: Pan-STARRS1 Discovery of a New Type of Superluminous Supernova

We present the Pan-STARRS1 discovery of PS1-10afx, a unique hydrogen-deficient superluminous supernova (SLSN) at redshift z = 1.388. The light curve peaked at z P1 = 21.7 mag, making PS1-10afx comparable to the most luminous known SNe, with Mu = –22.3 mag. Our extensive optical and near-infrared observations indicate that the bolometric light curve of PS1-10afx rose on the unusually fast timescale of ~12 days to the extraordinary peak luminosity of 4.1 × 1044 erg s–1 (M bol = –22.8 mag) and subsequently faded rapidly. Equally important, the spectral energy distribution is unusually red for an SLSN, with a color temperature of ~6800 K near maximum light, in contrast to previous hydrogen-poor SLSNe, which are bright in the ultraviolet (UV). The spectra more closely resemble those of a normal SN Ic than any known SLSN, with a photospheric velocity of ~11, 000 km s–1 and evidence for line blanketing in the rest-frame UV. Despite the fast rise, these parameters imply a very large emitting radius (gsim 5 × 1015 cm). We demonstrate that no existing theoretical model can satisfactorily explain this combination of properties: (1) a nickel-powered light curve cannot match the combination of high peak luminosity with the fast timescale; (2) models powered by the spindown energy of a rapidly rotating magnetar predict significantly hotter and faster ejecta; and (3) models invoking shock breakout through a dense circumstellar medium cannot explain the observed spectra or color evolution. The host galaxy is well detected in pre-explosion imaging with a luminosity near L*, a star formation rate of ~15 M ☉ yr–1, and is fairly massive (~2 × 1010 M ☉), with a stellar population age of ~108 yr, also in contrast to the young dwarf hosts of known hydrogen-poor SLSNe. PS1-10afx is distinct from known examples of SLSNe in its spectra, colors, light-curve shape, and host galaxy properties, suggesting that it resulted from a different channel than other hydrogen-poor SLSNe.Astronom

The Ultraviolet-bright, Slowly Declining Transient PS1-11af as a Partial Tidal Disruption Event

We present the Pan-STARRS1 discovery of the long-lived and blue transient PS1-11af, which was also detected by Galaxy Evolution Explorer with coordinated observations in the near-ultraviolet (NUV) band. PS1-11af is associated with the nucleus of an early type galaxy at redshift z = 0.4046 that exhibits no evidence for star formation or active galactic nucleus activity. Four epochs of spectroscopy reveal a pair of transient broad absorption features in the UV on otherwise featureless spectra. Despite the superficial similarity of these features to P-Cygni absorptions of supernovae (SNe), we conclude that PS1-11af is not consistent with the properties of known types of SNe. Blackbody fits to the spectral energy distribution are inconsistent with the cooling, expanding ejecta of a SN, and the velocities of the absorption features are too high to represent material in homologous expansion near a SN photosphere. However, the constant blue colors and slow evolution of the luminosity are similar to previous optically selected tidal disruption events (TDEs). The shape of the optical light curve is consistent with models for TDEs, but the minimum accreted mass necessary to power the observed luminosity is only ~0.002 M ☉, which points to a partial disruption model. A full disruption model predicts higher bolometric luminosities, which would require most of the radiation to be emitted in a separate component at high energies where we lack observations. In addition, the observed temperature is lower than that predicted by pure accretion disk models for TDEs and requires reprocessing to a constant, lower temperature. Three deep non-detections in the radio with the Very Large Array over the first two years after the event set strict limits on the production of any relativistic outflow comparable to Swift J1644+57, even if off-axis

Toward Characterization of the Type IIP Supernova Progenitor Population: A Statistical Sample of Light Curves from Pan-STARRS1

In recent years, wide-field sky surveys providing deep multiband imaging have presented a new path for indirectly characterizing the progenitor populations of core-collapse supernovae (SNe): systematic light-curve studies. We assemble a set of 76 grizy-band Type IIP SN light curves from Pan-STARRS1, obtained over a constant survey program of 4 yr and classified using both spectroscopy and machine-learning-based photometric techniques. We develop and apply a new Bayesian model for the full multiband evolution of each light curve in the sample. We find no evidence of a subpopulation of fast-declining explosions (historically referred to as "Type IIL" SNe). However, we identify a highly significant relation between the plateau phase decay rate and peak luminosity among our SNe IIP. These results argue in favor of a single parameter, likely determined by initial stellar mass, predominantly controlling the explosions of red supergiants. This relation could also be applied for SN cosmology, offering a standardizable candle good to an intrinsic scatter of lesssim 0.2 mag. We compare each light curve to physical models from hydrodynamic simulations to estimate progenitor initial masses and other properties of the Pan-STARRS1 Type IIP SN sample. We show that correction of systematic discrepancies between modeled and observed SN IIP light-curve properties and an expanded grid of progenitor properties are needed to enable robust progenitor inferences from multiband light-curve samples of this kind. This work will serve as a pathfinder for photometric studies of core-collapse SNe to be conducted through future wide-field transient searches.Astronom

Outcomes after extended azithromycin administration in preterm premature rupture of membranesAJOG Global Reports at a Glance

BACKGROUND: Preterm premature rupture of membranes accounts for approximately one-quarter of all preterm deliveries and occurs in 2% to 3% of all pregnancies. With subclinical infection being a suspected cause of preterm premature rupture of membranes, the administration of prophylactic antibiotics is an accepted standard of care to extend the latency period. Historically, erythromycin was used in the antibiotic regimen recommended for women with preterm premature rupture of membranes during expectant management; however, azithromycin has recently been shown to be a suitable alternative. OBJECTIVE: This study aimed to evaluate whether extended azithromycin administration affects the latency time in preterm premature rupture of membranes. STUDY DESIGN: This was a retrospective multi-institutional cohort study in Washington, District of Columbia, of patients admitted from January 2012 to December 2019 with preterm premature rupture of membranes of singleton pregnancies between 23 0/7 and 33 6/7 weeks of gestation. Patients were excluded if they had multiple pregnancies, had an allergy to penicillin or macrolides, were in labor, had suspected placental abruptions, had overt chorioamnionitis, or had nonreassuring fetal status on presentation indicating the need for prompt delivery. Patients that received limited azithromycin administration (3 days (2.6 days [interquartile range, 2.2–3.1] for limited azithromycin administration vs 5.8 days [interquartile range, 4.8–6.9] for extended azithromycin administration; P<.001). Neonatal secondary outcome evaluation was performed on 216 cases (76%). There was no difference in chorioamnionitis or adverse neonatal outcomes between the 2 groups. CONCLUSION: Among patients with preterm premature rupture of membranes, extended azithromycin administration was associated with increased latency, without any effect on other maternal or neonatal outcomes

Effects of Initial Abstinence and Programmed Lapses on The Relative Reinforcing Effects of Cigarette Smoking

Fifty-eight smokers received abstinence-contingent monetary payments for 1 (n  =  15) or 14 (n  =  43) days. Those who received contingent payments for 14 days also received 0, 1, or 8 experimenter-delivered cigarette puffs on 5 evenings. The relative reinforcing effects of smoking were assessed in a 3-hr session on the final study day, when participants made 20 choices between smoking or money. The reinforcement contingencies exerted robust control over smoking, and programmed smoking lapses produced few discernible effects. These results further illustrate the robust control that reinforcement contingencies can exert over cigarette smoking and suggest that any effects of lapses on the relative reinforcing effects of smoking are modest under conditions involving abstinence-contingent reinforcement contingencies

Ps1-12sk Is a Peculiar Supernova From a He-Rich Progenitor System in a Brightest Cluster Galaxy Environment

We report on our discovery and observations of the Pan-STARRS1 supernova (SN) PS1-12sk, a transient with properties that indicate atypical star formation in its host galaxy cluster or pose a challenge to popular progenitor system models for this class of explosion. The optical spectra of PS1- 12sk classify it as a Type Ibn SN (c.f. SN 2006jc), dominated by intermediate-width (3×103 km s−1) and time variable He I emission. Our multi-wavelength monitoring establishes the rise time dt ∼ 9 − 23 days and shows an NUV-NIR SED with temperature & 17 × 103 K and a peak magnitude of Mz = −18.88 ± 0.02 mag. SN Ibn spectroscopic properties are commonly interpreted as the signature of a massive star (17 − 100 M⊙) explosion within a He-enriched circumstellar medium. However, unlike previous Type Ibn supernovae, PS1-12sk is associated with an elliptical brightest cluster galaxy, CGCG 208-042 (z = 0.054) in cluster RXC J0844.9+4258. The expected probability of an event like PS1-12sk in such environments is low given the measured infrequency of core-collapse SNe in red sequence galaxies compounded by the low volumetric rate of SN Ibn. Furthermore, we find no evidence of star formation at the explosion site to sensitive limits (ΣHα . 2×10−3 M⊙ yr−1 kpc−2). We therefore discuss white dwarf binary systems as a possible progenitor channel for SNe Ibn. We conclude that PS1-12sk represents either a fortuitous and statistically unlikely discovery, evidence for a top-heavy IMF in galaxy cluster cooling flow filaments, or the first clue suggesting an alternate progenitor channel for Type Ibn SNe.Astronom

Ps1-10bzj: A Fast, Hydrogen-Poor Superluminous Supernova in a Metal Poor Host Galaxy

We present observations and analysis of PS1-10bzj, a superluminous supernova (SLSN) discovered in the Pan-STARRS Medium Deep Survey at a redshift z = 0.650. Spectroscopically, PS1-10bzj is similar to the hydrogen-poor SLSNe 2005ap and SCP 06F6, though with a steeper rise and lower peak luminosity (Mbol ≃ −21.4 mag) than previous events. We construct a bolometric light curve, and show that while PS1-10bzj’s energetics were less extreme than previous events, its luminosity still cannot be explained by radioactive nickel decay alone. We explore both a magnetar spin-down and circumstellar interaction scenario and find that either can fit the data. PS1-10bzj is located in the Extended Chandra Deep Field South and the host galaxy is imaged in a number of surveys, including with the Hubble Space Telescope. The host is a compact dwarf galaxy (MB ≈ −18 mag, diameter. 800 pc), with a low stellar mass (M∗ ≈ 2.4 × 107 M⊙), young stellar population (τ∗ ≈ 5 Myr), and a star formation rate of ∼ 2 − 3 M⊙ yr−1 . The specific star formation rate is the highest seen in an SLSN host so far (∼ 100 Gyr−1). We detect the [O III] λ4363 line, and find a low metallicity: 12+(O/H) = 7.8 ± 0.2 (≃ 0.1Z⊙). Together, this indicates that at least some of the progenitors of SLSNe come from young, low-metallicity populations.Astronom

Zooming in on the progenitors of superluminous supernovae with the HST

We present Hubble Space Telescope (HST) rest-frame ultraviolet imaging of the host galaxies of 16 hydrogen-poor superluminous supernovae (SLSNe), including 11 events from the Pan-STARRS Medium Deep Survey. Taking advantage of the superb angular resolution of HST, we characterize the galaxies' morphological properties, sizes, and star formation rate (SFR) densities. We determine the supernova (SN) locations within the host galaxies through precise astrometric matching and measure physical and host-normalized offsets as well as the SN positions within the cumulative distribution of UV light pixel brightness. We find that the host galaxies of H-poor SLSNe are irregular, compact dwarf galaxies, with a median half-light radius of just 0.9 kpc. The UV-derived SFR densities are high ($\langle {{{\Sigma }}_{{\rm SFR}}}\rangle \simeq 0.1{{M}_{\odot }}\;{\rm y}{{{\rm r}}^{-1}}\;{\rm kp}{{{\rm c}}^{-2}}$), suggesting that SLSNe form in overdense environments. Their locations trace the UV light of their host galaxies, with a distribution intermediate between that of long-duration gamma-ray bursts (LGRBs; which are strongly clustered on the brightest regions of their hosts) and a uniform distribution (characteristic of normal core-collapse SNe), though cannot be statistically distinguished from either with the current sample size. Taken together, this strengthens the picture that SLSN progenitors require different conditions than those of ordinary core-collapse SNe to form and that they explode in broadly similar galaxies as do LGRBs. If the tendency for SLSNe to be less clustered on the brightest regions than are LGRBs is confirmed by a larger sample, this would indicate a different, potentially lower-mass progenitor for SLSNe than LRGBs.Astronom

Rapidly evolving and luminous transients from Pan-STARRS1

In the past decade, several rapidly evolving transients have been discovered whose timescales and luminosities are not easily explained by traditional supernovae (SNe) models. The sample size of these objects has remained small due, at least in part, to the challenges of detecting short timescale transients with traditional survey cadences. Here we present the results from a search within the Pan-STARRS1 Medium Deep Survey (PS1-MDS) for rapidly evolving and luminous transients. We identify 10 new transients with a time above half-maximum (t 1/2) of less than 12 days and –16.5 > M > –20 mag. This increases the number of known events in this region of SN phase space by roughly a factor of three. The median redshift of the PS1-MDS sample is z = 0.275 and they all exploded in star-forming galaxies. In general, the transients possess faster rise than decline timescale and blue colors at maximum light (g P1 – r P1 lesssim –0.2). Best-fit blackbodies reveal photospheric temperatures/radii that expand/cool with time and explosion spectra taken near maximum light are dominated by a blue continuum, consistent with a hot, optically thick, ejecta. We find it difficult to reconcile the short timescale, high peak luminosity (L > 1043 erg s–1), and lack of UV line blanketing observed in many of these transients with an explosion powered mainly by the radioactive decay of 56Ni. Rather, we find that many are consistent with either (1) cooling envelope emission from the explosion of a star with a low-mass extended envelope that ejected very little (<0.03 M ☉) radioactive material, or (2) a shock breakout within a dense, optically thick, wind surrounding the progenitor star. After calculating the detection efficiency for objects with rapid timescales in the PS1-MDS we find a volumetric rate of 4800-8000 events yr–1 Gpc–3 (4%-7% of the core-collapse SN rate at z = 0.2).Astronom