GRB 081008: from burst to afterglow and the transition phase in between

We present a multi-wavelength study of GRB 081008, at redshift 1.967, by Swift, ROTSE-III and GROND. Compared to other Swift GRBs, GRB 081008 has a typical gamma-ray isotropic equivalent energy output (10^53 erg) during the prompt phase, and displayed two temporally separated clusters of pulses. The early X-ray emission seen by the Swift/XRT was dominated by the softening tail of the prompt emission, producing multiple flares during and after the Swift/BAT detections. Optical observations that started shortly after the first active phase of gamma-ray emission showed two consecutive peaks. We interpret the first optical peak as the onset of the afterglow associated with the early burst activities. A second optical peak, coincident with the later gamma-ray pulses, imposes a small modification to the otherwise smooth lightcurve and thus suggests a minimal contribution from a probable internal component. We suggest the early optical variability may be from continuous energy injection into the forward shock front by later shells producing the second epoch of burst activities. These early observations thus provide a potential probe for the transition from prompt to the afterglow phase. The later lightcurve of GRB 081008 displays a smooth steepening in all optical bands and X-ray. The temporal break is consistent with being achromatic at the observed wavelengths. Our broad energy coverage shortly after the break constrains a spectral break within optical. However, the evolution of the break frequency is not observed. We discuss the plausible interpretations of this behavior.Comment: 16 pages, 4 figures, accepted for publication in Ap

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 {{s}} with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of {40}-8+8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 {M}ȯ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 {{Mpc}}) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Addressing contact tracing challenges—critical to halting Ebola virus disease transmission

SummaryBackgroundDelayed and ineffective contact tracing contributed to the extensive transmission of Ebola virus disease (EVD) in the 2014–2015 West African outbreak. Understanding and addressing the challenges to implementing and managing contact tracing is essential to stopping EVD transmission and preventing large-scale EVD outbreaks in the future.MethodsInterviews were conducted with United States Centers for Disease Control and Prevention staff members engaged in contact tracing activities in the affected West African countries of Sierra Leone, Guinea, Liberia, Senegal, Nigeria, and Mali from September through December 2014. Two staff members from each country were interviewed. The five most frequently cited contact tracing challenges were identified.ResultsChallenges have been evident in every step of the contact tracing process from implementation to management, including identifying, locating, and enrolling contact-persons, as well as managing personnel and ensuring contact tracing performance. Common themes observed in all of the affected West African countries have included fear, stigma, and community misperceptions regarding EVD. Countries that have overcome these challenges, ensuring immediate and comprehensive contact tracing, have been successful in halting EVD transmission.ConclusionsAddressing challenges to contact tracing implementation and management in the West African EVD outbreak is essential to stopping ongoing transmission

Crimean-Congo Hemorrhagic Fever Knowledge, Attitudes, Practices, Risk Factors, and Seroprevalence in Rural Georgian Villages with Known Transmission in 2014.

In 2014 the highest annual case count of Crimean-Congo hemorrhagic fever (CCHF) was detected in Georgia since surveillance began in 2009. CCHF is a high-fatality hemorrhagic syndrome transmitted by infected ticks and animal blood. In response to this immediate public health threat, we assessed CCHF risk factors, seroprevalence, and CCHF-related knowledge, attitudes, and practices in the 12 rural villages reporting a 2014 CCHF case, to inform CCHF prevention and control measures. Households were randomly selected for interviewing and serum sample collection. Data were weighted by non-response and gender; percentages reflect weighting. Among 618 respondents, median age was 54.8 years (IQR: 26.5, range: 18.6-101.4); 215 (48.8%) were male. Most (91.5%) participants reported ≥1 CCHF high-risk activity. Of 389 participants with tick exposure, 286 (46.7%) participants handled ticks bare-handed; 65/216 (29.7%) knew the risk. Of 605 respondents, 355 (57.9%) reported animal blood exposure; 32/281 (12.7%) knew the risk. Of 612 responding, 184 (28.8%) knew protective measures against CCHF and tick exposures, but only 54.3% employed the measures. Of 435 serum samples collected, 12 were anti-CCHF IgG positive, indicating a weighted 3.0% seroprevalence. Most (66.7%) seropositive subjects reported tick exposure. In these villages, CCHF risk factors are prevalent, while CCHF-related knowledge and preventive practices are limited; these findings are critical to informing public health interventions to effectively control and prevent ongoing CCHF transmission. Additionally, CCHF seroprevalence is higher than previously detected (0.03%), highlighting the importance of this disease in the South Caucuses and in supporting ongoing regional investigations

Acute Q Fever Case Detection among Acute Febrile Illness Patients, Thailand, 2002-2005

International audienceAcute Q fever cases were identified from a hospital-based acute febrile illness study conducted in six community hospitals in rural north and northeast Thailand from 2002 to 2005. Of 1,784 participants that underwent Coxiella burnetii testing, nine (0.5%) participants were identified in this case-series as acute Q fever cases. Eight case-patients were located in one province. Four case-patients were hospitalized. Median age was 13 years (range: 7-69); five were male. The proportion of children with acute Q fever infection was similar to adults (P=0.17). This previously unrecognized at-risk group, school-age children, indicates that future studies and prevention interventions should target this population. The heterogeneity of disease burden across Thailand and milder clinical presentations found in this case-series should be considered in future studies. As diagnosis based on serology is limited during the acute phase of the disease, other diagnostic options, such as polymerase chain reaction, should be explored to improve acute case detection