| 1. |
- Bousquet, J, et al.
(author)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Journal article (peer-reviewed)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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| 2. |
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| 3. |
- Needham, E. J., et al.
(author)
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Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses
- 2022
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:11, s. 4097-4107
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Journal article (peer-reviewed)abstract
- COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity. We investigated the dynamics of, and relationship between, serum markers of brain injury [neurofilament light (NfL), glial fibrillary acidic protein (GFAP) and total tau] and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza. During hospitalization, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort. A distinct process characterized by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP. These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible. Needham et al. reveal elevations in blood biomarkers of brain injury in patients hospitalised with COVID-19. The changes, which were severity-dependent, were associated with dysregulated immune responses including increases in pro-inflammatory cytokines and autoantibodies. Ongoing active brain injury could still be seen months after infection.
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| 4. |
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| 7. |
- Brennan, Seán J., 1995-, et al.
(author)
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Spectroscopic observations of progenitor activity 100 days before a Type Ibn supernova
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
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Journal article (peer-reviewed)abstract
- Obtaining spectroscopic observations of the progenitors of core-collapse supernovae is often unfeasible, due to an inherent lack of knowledge as to what stars experience supernovae and when they will explode. In this Letter we present photometric and spectroscopic observations of the progenitor activity of SN 2023fyq before the He-rich progenitor explodes as a Type Ibn supernova. The progenitor of SN 2023fyq shows an exponential rise in flux prior to core collapse. Complex He I emission line features are observed in the progenitor spectra, with a P Cygni-like profile, as well as an evolving broad base with velocities of the order of 10 000 km s−1. The luminosity and evolution of SN 2023fyq is consistent with a Type Ibn, reaching a peak r-band magnitude of −18.8 mag, although there is some uncertainty regarding the distance to the host, NGC 4388, which is located in the Virgo cluster. We present additional evidence of asymmetric He-rich material being present both prior to and after the explosion of SN 2023fyq, which suggests that this material survived the ejecta interaction. Broad [O I], C I, and the Ca II triplet lines are observed at late phases, confirming that SN 2023fyq was a genuine supernova, rather than a non-terminal interacting transient. SN 2023fyq provides insight into the final moments of a massive star’s life, demonstrating that the progenitor is likely highly unstable before core collapse.
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| 8. |
- Gal-Yam, A., et al.
(author)
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A WC/WO star exploding within an expanding carbon-oxygen-neon nebula
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 601:7892, s. 201-204
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Journal article (peer-reviewed)abstract
- The final fate of massive stars, and the nature of the compact remnants they leave behind (black holes and neutron stars), are open questions in astrophysics. Many massive stars are stripped of their outer hydrogen envelopes as they evolve. Such Wolf-Rayet stars(1) emit strong and rapidly expanding winds with speeds greater than 1,000 kilometres per second. A fraction of this population is also helium-depleted, with spectra dominated by highly ionized emission lines of carbon and oxygen (types WC/WO). Evidence indicates that the most commonly observed supernova explosions that lack hydrogen and helium (types Ib/Ic) cannot result from massive WC/WO stars(2,3), leading some to suggest that most such stars collapse directly into black holes without a visible supernova explosion(4). Here we report observations of SN 2019hgp, beginning about a day after the explosion. Its short rise time and rapid decline place it among an emerging population of rapidly evolving transients(5-8). Spectroscopy reveals a rich set of emission lines indicating that the explosion occurred within a nebula composed of carbon, oxygen and neon. Narrow absorption features show that this material is expanding at high velocities (greater than 1,500 kilometres per second), requiring a compact progenitor. Our observations are consistent with an explosion of a massive WC/WO star, and suggest that massive Wolf-Rayet stars may be the progenitors of some rapidly evolving transients.
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| 9. |
- Palou, J., et al.
(author)
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Recurrence, progression and cancer-specific mortality according to stage at re-TUR in T1G3 bladder cancer patients treated with BCG : not as bad as previously thought
- 2018
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In: World journal of urology. - : SPRINGER. - 0724-4983 .- 1433-8726. ; 36:10, s. 1621-1627
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Journal article (peer-reviewed)abstract
- Purpose: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG.Methods: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model.Results:During a median follow-up of 5.2years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P<0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P<0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen.Conclusions: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease.
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| 10. |
- Soria, Francesco, et al.
(author)
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Predictors of oncological outcomes in T1G3 patients treated with BCG who undergo radical cystectomy
- 2018
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In: World journal of urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 36:11, s. 1775-1781
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Journal article (peer-reviewed)abstract
- Purpose: To evaluate the oncological impact of postponing radical cystectomy (RC) to allow further conservative therapies prior to progression in a large multicentre retrospective cohort of T1-HG/G3 patients initially treated with BCG.Methods: According to the time of RC, the population was divided into 3 groups: patients who did not progress to muscle-invasive disease, patients who progressed before radical cystectomy and patients who experienced progression at the time of radical cystectomy. Clinical and pathological outcomes were compared across the three groups.Results: Of 2451 patients, 509 (20.8%) underwent RC. Patients with tumors > 3 cm or with CIS had earlier cystectomies (HR = 1.79, p = 0.001 and HR = 1.53, p = 0.02, respectively). Patients with tumors > 3 cm, multiple tumors or CIS had earlier T3/T4 or N + cystectomies. In patients who progressed, the timing of cystectomy did not affect the risk of T3/T4 or N + disease at RC. Patients with T3/T4 or N + disease at RC had a shorter disease-specific survival (HR = 4.38, p < 0.001), as did patients with CIS at cystectomy (HR = 2.39, p < 0.001). Patients who progressed prior to cystectomy had a shorter disease-specific survival than patients for whom progression was only detected at cystectomy (HR = 0.58, p = 0.024)Conclusions: Patients treated with RC before experiencing progression to muscle-invasive disease harbor better oncological and survival outcomes compared to those who progressed before RC and to those upstaged at surgery. Tumor size and concomitant CIS at diagnosis are the main predictors of surgical treatment while tumor size, CIS and tumor multiplicity are associated with extravesical disease at surgery.
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| 11. |
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| 12. |
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| 13. |
- Pisano, F., et al.
(author)
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Risk factors for residual disease at re-TUR in a large cohort of T1G3 patients
- 2021
-
In: Actas Urológicas Españolas. - : ENE EDICIONES SL. - 0210-4806 .- 1699-7980. ; 45:6, s. 473-478
-
Journal article (peer-reviewed)abstract
- Introduction and objectives: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR.Material and methods: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions.Results: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors >= 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001.Conclusions: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.
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| 14. |
- Pisano, F, et al.
(author)
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Risk factors for residual disease at re-TUR in a large cohort of T1G3 patients.
- 2021
-
In: Actas urologicas espanolas. - : Elsevier BV. - 2173-5786. ; 45:6, s. 473-478
-
Journal article (peer-reviewed)abstract
- INTRODUCTION AND OBJECTIVES: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR.MATERIAL AND METHODS: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions.RESULTS: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors > 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001.CONCLUSIONS: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.
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| 15. |
- Miller, A. A., et al.
(author)
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The Spectacular Ultraviolet Flash from the Peculiar Type Ia Supernova 2019yvq
- 2020
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 898:1
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Journal article (peer-reviewed)abstract
- Early observations of Type Ia supernovae (SNe Ia) provide essential clues for understanding the progenitor system that gave rise to the terminal thermonuclear explosion. We present exquisite observations of SN 2019yvq, the second observed SN Ia, after iPTF 14atg, to display an early flash of emission in the ultraviolet (UV) and optical. Our analysis finds that SN 2019yvq was unusual, even when ignoring the initial flash, in that it was moderately underluminous for an SN Ia ( mag at peak) yet featured very high absorption velocities ( km s−1 for Si ii λ6355 at peak). We find that many of the observational features of SN 2019yvq, aside from the flash, can be explained if the explosive yield of radioactive 56Ni is relatively low (we measure ) and it and other iron-group elements are concentrated in the innermost layers of the ejecta. To explain both the UV/optical flash and peak properties of SN 2019yvq we consider four different models: interaction between the SN ejecta and a nondegenerate companion, extended clumps of 56Ni in the outer ejecta, a double-detonation explosion, and the violent merger of two white dwarfs. Each of these models has shortcomings when compared to the observations; it is clear additional tuning is required to better match SN 2019yvq. In closing, we predict that the nebular spectra of SN 2019yvq will feature either H or He emission, if the ejecta collided with a companion, strong [Ca ii] emission, if it was a double detonation, or narrow [O i] emission, if it was due to a violent merger.
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| 16. |
- Nicholl, M., et al.
(author)
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An outflow powers the optical rise of the nearby, fast-evolving tidal disruption event AT2019qiz
- 2020
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 499:1, s. 482-504
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Journal article (peer-reviewed)abstract
- At 66 Mpc, AT2019qiz is the closest optical tidal disruption event (TDE) to date, with a luminosity intermediate between the bulk of the population and the faint-and-fast event iPTF16fnl. Its proximity allowed a very early detection and triggering of multiwavelength and spectroscopic follow-up well before maximum light. The velocity dispersion of the host galaxy and fits to the TDE light curve indicate a black hole mass approximate to 10(6) M-circle dot, disrupting a star of approximate to 1 M-circle dot. By analysing our comprehensive UV, optical, and X-ray data, we show that the early optical emission is dominated by an outflow, with a luminosity evolution L proportional to t(2), consistent with a photosphere expanding at constant velocity (greater than or similar to 2000 km s(-1)), and a line-forming region producing initially blueshifted H and He II profiles with v = 3000-10 000 km s(-1). The fastest optical ejecta approach the velocity inferred from radio detections (modelled in a forthcoming companion paper from K. D. Alexander et al.), thus the same outflow may be responsible for both the fast optical rise and the radio emission - the first time this connection has been observed in a TDE. The light-curve rise begins 29 +/- 2 d before maximum light, peaking when the photosphere reaches the radius where optical photons can escape. The photosphere then undergoes a sudden transition, first cooling at constant radius then contracting at constant temperature. At the same time, the blueshifts disappear from the spectrum and Bowen fluorescence lines (N III) become prominent, implying a source of far-UV photons, while the X-ray light curve peaks at approximate to 10(41) erg s(-1). Assuming that these X-rays are from prompt accretion, the size and mass of the outflow are consistent with the reprocessing layer needed to explain the large optical to X-ray ratio in this and other optical TDEs, possibly favouring accretion-powered over collision-powered outflow models.
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| 17. |
- Perley, Daniel A., et al.
(author)
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The Zwicky Transient Facility Bright Transient Survey. II. A Public Statistical Sample for Exploring Supernova Demographics
- 2020
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 904:1
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Journal article (peer-reviewed)abstract
- We present a public catalog of transients from the Zwicky Transient Facility (ZTF) Bright Transient Survey, a magnitude-limited (m g or r filter) survey for extragalactic transients in the ZTF public stream. We introduce cuts on survey coverage, sky visibility around peak light, and other properties unconnected to the nature of the transient, and show that the resulting statistical sample is spectroscopically 97% complete at <18 mag, 93% complete at <18.5 mag, and 75% complete at <19 mag. We summarize the fundamental properties of this population, identifying distinct duration-luminosity correlations in a variety of supernova (SN) classes and associating the majority of fast optical transients with well-established spectroscopic SN types (primarily SN Ibn and II/IIb). We measure the Type Ia SN and core-collapse (CC) SN rates and luminosity functions, which show good consistency with recent work. About 7% of CC SNe explode in very low-luminosity galaxies (M-i > -16 mag), 10% in red-sequence galaxies, and 1% in massive ellipticals. We find no significant difference in the luminosity or color distributions between the host galaxies of SNe Type II and SNe Type Ib/c, suggesting that line-driven wind stripping does not play a major role in the loss of the hydrogen envelope from their progenitors. Future large-scale classification efforts with ZTF and other wide-area surveys will provide high-quality measurements of the rates, properties, and environments of all known types of optical transients and limits on the existence of theoretically predicted but as yet unobserved explosions.
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| 18. |
- Bruch, Rachel J., et al.
(author)
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A Large Fraction of Hydrogen-rich Supernova Progenitors Experience Elevated Mass Loss Shortly Prior to Explosion
- 2021
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 912:1
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Journal article (peer-reviewed)abstract
- Spectroscopic detection of narrow emission lines traces the presence of circumstellar mass distributions around massive stars exploding as core-collapse supernovae. Transient emission lines disappearing shortly after the supernova explosion suggest that the material spatial extent is compact and implies an increased mass loss shortly prior to explosion. Here, we present a systematic survey for such transient emission lines (Flash Spectroscopy) among Type II supernovae detected in the first year of the Zwicky Transient Facility survey. We find that at least six out of ten events for which a spectrum was obtained within two days of the estimated explosion time show evidence for such transient flash lines. Our measured flash event fraction (>30% at 95% confidence level) indicates that elevated mass loss is a common process occurring in massive stars that are about to explode as supernovae.
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| 19. |
- Bruch, Rachel J., et al.
(author)
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The Prevalence and Influence of Circumstellar Material around Hydrogen-rich Supernova Progenitors
- 2023
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 952:2
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Journal article (peer-reviewed)abstract
- Narrow transient emission lines (flash-ionization features) in early supernova (SN) spectra trace the presence of circumstellar material (CSM) around the massive progenitor stars of core-collapse SNe. The lines disappear within days after the SN explosion, suggesting that this material is spatially confined, and originates from enhanced mass loss shortly (months to a few years) prior to the explosion. We performed a systematic survey of H-rich (Type II) SNe discovered within less than 2 days from the explosion during the first phase of the Zwicky Transient Facility survey (2018–2020), finding 30 events for which a first spectrum was obtained within <2 days from the explosion. The measured fraction of events showing flash-ionization features (>36% at the 95% confidence level) confirms that elevated mass loss in massive stars prior to SN explosion is common. We find that SNe II showing flash-ionization features are not significantly brighter, nor bluer, nor more slowly rising than those without. This implies that CSM interaction does not contribute significantly to their early continuum emission, and that the CSM is likely optically thin. We measured the persistence duration of flash-ionization emission and find that most SNe show flash features for ≈5 days. Rarer events, with persistence timescales >10 days, are brighter and rise longer, suggesting these may be intermediate between regular SNe II and strongly interacting SNe IIn.
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| 20. |
- Gontero, Paolo, et al.
(author)
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The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guérin
- 2016
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In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 118:1, s. 44-52
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS).PATIENTS AND METHODS: In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette-Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups.RESULTS: Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints.CONCLUSIONS: Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR.
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| 21. |
- Irani, I., et al.
(author)
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Less Than 1% of Core-collapse Supernovae in the Local Universe Occur in Elliptical Galaxies
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 927:1
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Journal article (peer-reviewed)abstract
- We present observations of three core-collapse supernovae (CCSNe) in elliptical hosts, detected by the Zwicky Transient Facility Bright Transient Survey (BTS). SN 2019ape is a SN Ic that exploded in the main body of a typical elliptical galaxy. Its properties are consistent with an explosion of a regular SN Ic progenitor. A secondary g-band light-curve peak could indicate interaction of the ejecta with circumstellar material (CSM). An Ha-emitting source at the explosion site suggests a residual local star formation origin. SN 2018fsh and SN 2020uik are SNe II which exploded in the outskirts of elliptical galaxies. SN 2020uik shows typical spectra for SNe II, while SN 2018fsh shows a boxy nebular Ha profile, a signature of CSM interaction. We combine these 3 SNe with 7 events from the literature and analyze their hosts as a sample. We present multi-wavelength photometry of the hosts, and compare this to archival photometry of all BTS hosts. Using the spectroscopically complete BTS, we conclude that 0.3%(+0.3)(-0.1) of all CCSNe occur in elliptical galaxies. We derive star formation rates and stellar masses for the host galaxies and compare them to the properties of other SN hosts. We show that CCSNe in ellipticals have larger physical separations from their hosts compared to SNe Ia in elliptical galaxies, and discuss implications for star-forming activity in elliptical galaxies.
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| 22. |
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| 23. |
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| 24. |
- Soumagnac, Maayane T., et al.
(author)
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SN 2018fif : The Explosion of a Large Red Supergiant Discovered in Its Infancy by the Zwicky Transient Facility
- 2020
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 902:1
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Journal article (peer-reviewed)abstract
- High-cadence transient surveys are able to capture supernovae closer to their first light than ever before. Applying analytical models to such early emission, we can constrain the progenitor stars' properties. In this paper, we present observations of SN 2018fif (ZTF 18abokyfk). The supernova was discovered close to first light and monitored by the Zwicky Transient Facility (ZTF) and the Neil Gehrels Swift Observatory. Early spectroscopic observations suggest that the progenitor of SN 2018fif was surrounded by relatively small amounts of circumstellar material compared to all previous cases. This particularity, coupled with the high-cadence multiple-band coverage, makes it a good candidate to investigate using shock-cooling models. We employ the SOPRANOS code, an implementation of the model by Sapir & Waxman and its extension to early times by Morag et al. Compared with previous implementations, SOPRANOS has the advantage of including a careful account of the limited temporal validity domain of the shock-cooling model as well as allowing usage of the entirety of the early UV data. We find that the progenitor of SN 2018fif was a large red supergiant with a radius of R = 744.0(-128.0)(+183.0) R-circle dot and an ejected mass of M-ej = 9.3(-5.8)(+0.4) M-circle dot. Our model also gives information on the explosion epoch, the progenitor's inner structure, the shock velocity, and the extinction. The distribution of radii is double-peaked, with smaller radii corresponding to lower values of the extinction, earlier recombination times, and a better match to the early UV data. If these correlations persist in future objects, denser spectroscopic monitoring constraining the time of recombination, as well as accurate UV observations (e.g., with ULTRASAT), will help break the extinction/radius degeneracy and independently determine both.
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| 25. |
- Damato, V, et al.
(author)
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Rituximab abrogates aquaporin-4-specific germinal center activity in patients with neuromyelitis optica spectrum disorders
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:24, s. e2121804119-
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Journal article (peer-reviewed)abstract
- By studying paired blood and deep cervical lymph node samples from patients with neuromyelitis optica spectrum disorders, our data provide evidence for a germinal center–based generation of aquaporin-4 antibodies. Frequent serum aquaporin-4 immunoglobulin Ms (IgMs) and shifts in IgG subclasses were observed alongside preferential synthesis of aquaporin-4 IgGs and aquaporin-4–reactive B cells within lymph nodes. Both intranodal synthesis of aquaporin-4 antibodies and intranodal aquaporin-4–reactive B cells were robustly eliminated with rituximab administration. This study systematically explores lymph nodes that drain the central nervous system (CNS) in patients with CNS autoimmunity and offers a potential explanation as to why rituximab is clinically highly efficacious in autoantibody-mediated diseases despite no accompanying reduction in serum autoantibody levels.
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| 26. |
- De, Kishalay, et al.
(author)
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The Zwicky Transient Facility Census of the Local Universe. I. Systematic Search for Calcium-rich Gap Transients Reveals Three Related Spectroscopic Subclasses
- 2020
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 905:1
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Journal article (peer-reviewed)abstract
- Using the Zwicky Transient Facility alert stream, we are conducting a large spectroscopic campaign to construct a complete, volume-limited sample of transients brighter than 20 mag, and coincident within 100 '' of galaxies in the Census of the Local Universe catalog. We describe the experiment design and spectroscopic completeness from the first 16 months of operations, which have classified 754 supernovae. We present results from a systematic search for calcium-rich gap transients in the sample of 22 low-luminosity (peak absolute magnitude M > -17), hydrogen-poor events found in the experiment. We report the detection of eight new events, and constrain their volumetric rate to greater than or similar to 15% +/- 5% of the SN Ia rate. Combining this sample with 10 previously known events, we find a likely continuum of spectroscopic properties ranging from events with SN Ia-like features (Ca-Ia objects) to those with SN Ib/c-like features (Ca-Ib/c objects) at peak light. Within the Ca-Ib/c events, we find two populations distinguished by their red (g - r approximate to 1.5 mag) or green (g - r approximate to 0.5 mag) colors at the r-band peak, wherein redder events show strong line blanketing features and slower light curves (similar to Ca-Ia objects), weaker He lines, and lower [Ca II]/[O I] in the nebular phase. We find that all together the spectroscopic continuum, volumetric rates, and striking old environments are consistent with the explosive burning of He shells on low-mass white dwarfs. We suggest that Ca-Ia and red Ca-Ib/c objects arise from the double detonation of He shells, while green Ca-Ib/c objects are consistent with low-efficiency burning scenarios like detonations in low-density shells or deflagrations.
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| 27. |
- Gontero, Paolo, et al.
(author)
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Prognostic Factors and Risk Groups in T1G3 Non-Muscle-invasive Bladder Cancer Patients Initially Treated with Bacillus Calmette-Guerin : Results of a Retrospective Multicenter Study of 2451 Patients
- 2015
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 67:1, s. 74-82
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Journal article (peer-reviewed)abstract
- Background: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. Objective: To assess prognostic factors in patients who received bacillus Calmette Guerin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. Design, setting, and participants: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. Outcome measurements and statistical analysis: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). Results and limitations: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age >= 70 yr, size >= 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients >= 70 yr with tumor size >= 3 cm and 13% otherwise. Conclusions: T1G3 patients >= 70 yr with tumors >= 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. Patient summary: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guerin, there is a subgroup of T1G3 patients with age >= 70 yr, tumor size >= 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.
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| 28. |
- Sharma, Yashvi, et al.
(author)
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A Systematic Study of Ia-CSM Supernovae from the ZTF Bright Transient Survey
- 2023
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 948:1
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Journal article (peer-reviewed)abstract
- Among the supernovae (SNe) that show strong interaction with a circumstellar medium (CSM), there is a rare subclass of Type Ia supernovae, SNe Ia-CSM, which show strong narrow hydrogen emission lines much like SNe IIn but on top of a diluted Type Ia spectrum. The only previous systematic study of this class identified 16 SNe Ia-CSM, eight historic and eight from the Palomar Transient Factory (PTF). Now using the successor survey to PTF, the Zwicky Transient Facility (ZTF), we have classified 12 additional SNe Ia-CSM through the systematic Bright Transient Survey (BTS). Consistent with previous studies, we find these SNe to have slowly evolving optical light curves with peak absolute magnitudes between -19.1 and -21, spectra having weak H ss and large Balmer ldecrements of similar to 7. Out of the 10 SNe from our sample observed by NEOWISE, nine have 3 sigma detections, with some SNe showing a reduction in the red wing of Ha, indicative of newly formed dust. We do not find our SN Ia-CSM sample to have a significantly different distribution of equivalent widths of He I.5876 than SNe IIn as observed in Silverman et al. The hosts tend to be late-type galaxies with recent star formation. We derive a rate estimate of 29+(27)(21) Gpc(-3) yr(-1) for SNe Ia-CSM, which is similar to 0.02%-0.2% of the SN Ia rate. We also identify six ambiguous SNe IIn/Ia-CSM in the BTS sample and including them gives an upper limit rate of 0.07%-0.8%. This work nearly doubles the sample of well-studied Ia-CSM objects in Silverman et al., increasing the total number to 28.
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| 29. |
- Witjes, J Alfred, et al.
(author)
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The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer
- 2016
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In: Urologic Oncology. - : Elsevier BV. - 1078-1439 .- 1873-2496. ; 34:11
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Journal article (peer-reviewed)abstract
- BACKGROUND: Potential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage.OBJECTIVE: To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients.DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival.RESULTS AND LIMITATIONS: Information on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20-1.82; P<0.001). With maintenance, TICE was more effective than Connaught for the time to first recurrence (HR = 0.66; 95% CI: 0.47-0.93; P = 0.019) with a trend for cancer specific survival (HR = 0.36; 95% CI: 0.14-0.92; P = 0.033). For time to progression and overall survival, Connaught and TICE had a similar efficacy. Compared to no maintenance therapy, maintenance BCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught.CONCLUSIONS: We found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given.PATIENT SUMMARY: As there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate compared to BCG TICE when no maintenance is used, but the opposite is true when maintenance is given.
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| 30. |
- Chen, Ping, et al.
(author)
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A 12.4-day periodicity in a close binary system after a supernova
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 253-258
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Journal article (peer-reviewed)abstract
- Neutron stars and stellar-mass black holes are the remnants of massive star explosions1. Most massive stars reside in close binary systems2, and the interplay between the companion star and the newly formed compact object has been theoretically explored3, but signatures for binarity or evidence for the formation of a compact object during a supernova explosion are still lacking. Here we report a stripped-envelope supernova, SN 2022jli, which shows 12.4-day periodic undulations during the declining light curve. Narrow Hα emission is detected in late-time spectra with concordant periodic velocity shifts, probably arising from hydrogen gas stripped from a companion and accreted onto the compact remnant. A new Fermi-LAT γ-ray source is temporally and positionally consistent with SN 2022jli. The observed properties of SN 2022jli, including periodic undulations in the optical light curve, coherent Hα emission shifting and evidence for association with a γ-ray source, point to the explosion of a massive star in a binary system leaving behind a bound compact remnant. Mass accretion from the companion star onto the compact object powers the light curve of the supernova and generates the γ-ray emission.
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| 31. |
- D'Andrea, David, et al.
(author)
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Association of patients' sex with treatment outcomes after intravesical bacillus Calmette-Guerin immunotherapy for T1G3/HG bladder cancer
- 2021
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In: World journal of urology. - : Springer Nature. - 0724-4983 .- 1433-8726. ; 39:9, s. 3337-3344
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Journal article (peer-reviewed)abstract
- Purpose: To investigate the association of patients' sex with recurrence and disease progression in patients treated with intravesical bacillus Calmette-Guerin (BCG) for T1G3/HG urinary bladder cancer (UBC).Materials and methods: We analyzed the data of 2635 patients treated with adjuvant intravesical BCG for T1 UBC between 1984 and 2019. We accounted for missing data using multiple imputations and adjusted for covariate imbalance between males and females using inverse probability weighting (IPW). Crude and IPW-adjusted Cox regression analyses were used to estimate the hazard ratios (HR) with their 95% confidence intervals (CI) for the association of patients' sex with HG-recurrence and disease progression.Results: A total of 2170 (82%) males and 465 (18%) females were available for analysis. Overall, 1090 (50%) males and 244 (52%) females experienced recurrence, and 391 (18%) males and 104 (22%) females experienced disease progression. On IPW-adjusted Cox regression analyses, female sex was associated with disease progression (HR 1.25, 95%CI 1.01-1.56, p = 0.04) but not with recurrence (HR 1.06, 95%CI 0.92-1.22, p = 0.41). A total of 1056 patients were treated with adequate BCG. In these patients, on IPW-adjusted Cox regression analyses, patients' sex was not associated with recurrence (HR 0.99, 95%CI 0.80-1.24, p = 0.96), HG-recurrence (HR 1.00, 95%CI 0.78-1.29, p = 0.99) or disease progression (HR 1.12, 95%CI 0.78-1.60, p = 0.55).Conclusion: Our analysis generates the hypothesis of a differential response to BCG between males and females if not adequately treated. Further studies should focus on sex-based differences in innate and adaptive immune system and their association with BCG response.
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| 32. |
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| 33. |
- Irani, Ido, et al.
(author)
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On the Origin of SN 2016hil-A Type II Supernova in the Remote Outskirts of an Elliptical Host
- 2019
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 887:2
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Journal article (peer-reviewed)abstract
- Type II supernovae (SNe) stem from the core collapse of massive (>8 M-circle dot) stars. Due to their short lifespan, we expect a very low rate of such events in elliptical hosts, where the star formation rate is low, and which are mostly comprised of an old stellar population. SN 2016hil (iPTF16hil) is an SN II located in the extreme outskirts of an elliptical galaxy at z.=.0.0608 (projected distance 27.2 kpc). It was detected near peak (M-r similar to -17 mag) 9 days after the last non-detection. The event has some potentially peculiar properties: it presented an apparently double-peaked light curve, and its spectra suggest low metallicity content (Z < 0.4 Z(circle dot)). We place a tentative upper limit on the mass of a potential faint host at log M/M-circle dot = 7.27(-0.24)(+0.43) using deep optical imaging from Keck/LRIS. In light of this, we discuss the possibility of the progenitor forming locally and other more exotic formation scenarios such as a merger or common-envelope evolution causing a time-delayed explosion. Further observations of the explosion site in the UV are needed in order to distinguish between the cases. Regardless of the origin of the transient, observing a population of such seemingly hostless SNe II could have many uses, including an estimate the amount of faint galaxies in a given volume, and tests of the prediction of a time-delayed population of core-collapse SNe in locations otherwise unfavorable for the detection of such events.
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| 34. |
- Irani, Ido, et al.
(author)
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SN 2022oqm-A Ca-rich Explosion of a Compact Progenitor Embedded in C/O Circumstellar Material
- 2024
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 962:2
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Journal article (peer-reviewed)abstract
- We present the discovery and analysis of SN 2022oqm, a Type Ic supernova (SN) detected <1 day after the explosion. The SN rises to a blue and short-lived (2 days) initial peak. Early-time spectral observations of SN 2022oqm show a hot (40,000 K) continuum with high ionization C and O absorption features at velocities of 4000 km s−1, while its photospheric radius expands at 20,000 km s−1, indicating a pre-existing distribution of expanding C/O material. After ∼2.5 days, both the spectrum and light curves evolve into those of a typical SN Ic, with line velocities of ∼10,000 km s−1, in agreement with the evolution of the photospheric radius. The optical light curves reach a second peak at t ≈ 15 days. By t = 60 days, the spectrum of SN 2022oqm becomes nearly nebular, displaying strong Ca ii and [Ca ii] emission with no detectable [O i], marking this event as Ca-rich. The early behavior can be explained by 10−3M⊙ of optically thin circumstellar material (CSM) surrounding either (1) a massive compact progenitor such as a Wolf–Rayet star, (2) a massive stripped progenitor with an extended envelope, or (3) a binary system with a white dwarf. We propose that the early-time light curve is powered by both the interaction of the ejecta with the optically thin CSM and shock cooling (in the massive star scenario). The observations can be explained by CSM that is optically thick to X-ray photons, is optically thick in the lines as seen in the spectra, and is optically thin to visible-light continuum photons that come either from downscattered X-rays or from the shock-heated ejecta. Calculations show that this scenario is self-consistent.
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| 35. |
- Irani, Mudar Zand, et al.
(author)
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Neutrophils, eosinophils, and intraepithelial lymphocytes in the squamous esophagus in subjects with and without gastroesophageal reflux symptoms
- 2021
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In: Human Pathology. - : Elsevier BV. - 0046-8177 .- 1532-8392. ; 115, s. 112-122
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Journal article (peer-reviewed)abstract
- Whilst intraepithelial lymphocytes (IELs) are considered normal within the distal esophageal mucosa, they have an increasingly recognised role in the pathogenesis of reflux esophagitis, and IEL quantification establishes the diagnosis of lymphocytic esophagitis. Knowledge regarding the upper limit of a normal IEL count in health is lacking. We studied 117 non-healthcare seeking adult volunteers from a random community sample (the Kalixanda study) with esophageal biopsies 2 cm above the gastroesophageal junction. Subjects were divided into four groups based on the presence or absence of gastro-esophageal reflux symptoms and/or esophagitis on endoscopy. Asymptomatic subjects with no endoscopic esophagitis were selected as controls, and the cell counts in this group were used to define the upper limit of normal of IELs, eosinophils and neutrophils. The entire sample was used to identify independent predictors of increased cellular counts by logistic regression analysis. None of the healthy controls had an IEL count of more than three per five high power fields (HPF), and therefore this was considered as the upper limit of normal; no controls had eosinophils or neutrophils in esophageal biopsies. Independent predictors of an elevated IEL count were spongiosis on histology (OR 11.17, 95% CI 3.32–37.58, P < 0.01) and current smoking (OR 4.84, 95% CI 1.13–2.71, P = 0.03). A receiver operating characteristics analysis concluded that a threshold of 3 IELs/5HPFs performs best in predicting reflux symptoms when a normal esophageal mucosa is visualized on endoscopy (sensitivity = 100.0%, specificity = 35.2%). The healthy esophageal mucosa does not contain more than three IELs per five HPF in the distal esophagus.
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| 36. |
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| 37. |
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| 38. |
- Perley, Daniel A., et al.
(author)
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The Type Icn SN 2021csp : Implications for the Origins of the Fastest Supernovae and the Fates of Wolf-Rayet Stars
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 927:2
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Journal article (peer-reviewed)abstract
- We present observations of SN 2021csp, the second example of a newly identified type of supernova (SN) hallmarked by strong, narrow, P Cygni carbon features at early times (Type Icn). The SN appears as a fast and luminous blue transient at early times, reaching a peak absolute magnitude of −20 within 3 days due to strong interaction between fast SN ejecta (v ≈ 30,000 km s−1) and a massive, dense, fast-moving C/O wind shed by the WC-like progenitor months before explosion. The narrow-line features disappear from the spectrum 10–20 days after explosion and are replaced by a blue continuum dominated by broad Fe features, reminiscent of Type Ibn and IIn supernovae and indicative of weaker interaction with more extended H/He-poor material. The transient then abruptly fades ∼60 days post-explosion when interaction ceases. Deep limits at later phases suggest minimal heavy-element nucleosynthesis, a low ejecta mass, or both, and imply an origin distinct from that of classical Type Ic SNe. We place SN 2021csp in context with other fast-evolving interacting transients, and discuss various progenitor scenarios: an ultrastripped progenitor star, a pulsational pair-instability eruption, or a jet-driven fallback SN from a Wolf–Rayet (W-R) star. The fallback scenario would naturally explain the similarity between these events and radio-loud fast transients, and suggests a picture in which most stars massive enough to undergo a W-R phase collapse directly to black holes at the end of their lives.
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| 39. |
- Strotjohann, Nora L., et al.
(author)
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Bright, Months-long Stellar Outbursts Announce the Explosion of Interaction-powered Supernovae
- 2021
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 907:2
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Journal article (peer-reviewed)abstract
- Interaction-powered supernovae (SNe) explode within an optically thick circumstellar medium (CSM) that could be ejected during eruptive events. To identify and characterize such pre-explosion outbursts, we produce forced-photometry light curves for 196 interacting SNe, mostly of Type IIn, detected by the Zwicky Transient Facility between early 2018 and 2020 June. Extensive tests demonstrate that we only expect a few false detections among the 70,000 analyzed pre-explosion images after applying quality cuts and bias corrections. We detect precursor eruptions prior to 18 Type IIn SNe and prior to the Type Ibn SN 2019uo. Precursors become brighter and more frequent in the last months before the SN and month-long outbursts brighter than magnitude -13 occur prior to 25% (5-69%, 95% confidence range) of all Type IIn SNe within the final three months before the explosion. With radiative energies of up to 10(49) erg, precursors could eject similar to 1 M of material. Nevertheless, SNe with detected precursors are not significantly more luminous than other SNe IIn, and the characteristic narrow hydrogen lines in their spectra typically originate from earlier, undetected mass-loss events. The long precursor durations require ongoing energy injection, and they could, for example, be powered by interaction or by a continuum-driven wind. Instabilities during the neon- and oxygen-burning phases are predicted to launch precursors in the final years to months before the explosion; however, the brightest precursor is 100 times more energetic than anticipated.
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Wilder-Smith, Annelies, et al.
(author)
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Zika vaccines and therapeutics : landscape analysis and challenges ahead
- 2018
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In: BMC Medicine. - : BioMed Central. - 1741-7015. ; 16
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Journal article (peer-reviewed)abstract
- BACKGROUND: Various Zika virus (ZIKV) vaccine candidates are currently in development. Nevertheless, unique challenges in clinical development and regulatory pathways may hinder the licensure of high-quality, safe, and effective ZIKV vaccines.DISCUSSION: Implementing phase 3 efficacy trials will be difficult given the challenges of the spatio-temporal heterogeneity of ZIKV transmission, the unpredictability of ZIKV epidemics, the broad spectrum of clinical manifestations making a single definite endpoint difficult, a lack of sensitive and specific diagnostic assays, and the need for inclusion of vulnerable target populations. In addition to a vaccine, drugs for primary prophylaxis, post-exposure prophylaxis, or treatment should also be developed to prevent or mitigate the severity of congenital Zika syndrome.CONCLUSION: Establishing the feasibility of immune correlates and/or surrogates are a priority. Given the challenges in conducting phase 3 trials at a time of waning incidence, human challenge trials should be considered to evaluate efficacy. Continued financial support and engagement of industry partners will be essential to the successful development, licensure, and accessibility of Zika vaccines or therapeutics.
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