The MiniBooNE Collaboration observes unexplained electronlike events in the reconstructed neutrino energy range from 200 to 475 MeV. With 6.46x10;{20} protons on target, 544 electronlike events are ...observed in this energy range, compared to an expectation of 415.2+/-43.4 events, corresponding to an excess of 128.8+/-20.4+/-38.3 events. The shape of the excess in several kinematic variables is consistent with being due to either nu_{e} and nuover _{e} charged-current scattering or nu_{mu} neutral-current scattering with a photon in the final state. No significant excess of events is observed in the reconstructed neutrino energy range from 475 to 1250 MeV, where 408 events are observed compared to an expectation of 385.9+/-35.7 events.
We report the observation of 16 cosmic ray events with a mean energy of 1.5 × 10¹⁹ eV via radio pulses originating from the interaction of the cosmic ray air shower with the Antarctic geomagnetic ...field, a process known as geosynchrotron emission. We present measurements in the 300-900 MHz range, which are the first self-triggered, first ultrawide band, first far-field, and the highest energy sample of cosmic ray events collected with the radio technique. Their properties are inconsistent with current ground-based geosynchrotron models. The emission is 100% polarized in the plane perpendicular to the projected geomagnetic field. Fourteen events are seen to have a phase inversion due to reflection of the radio beam off the ice surface, and two additional events are seen directly from above the horizon. Based on a likelihood analysis, we estimate angular pointing precision of order 2° for the event arrival directions.
Summary Background The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant ...vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log10 dose range in two sequential cohorts. Methods In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18–61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 103 , 3 × 104 , 3 × 105 , or 3 × 106 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 106 , 9 × 106 , 2 × 107 , or 1 × 108 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov , number NCT02314923. Findings Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 103 n=64, 3 × 104 n=64, 3 × 105 n=64, or 3 × 106 PFU n=64) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 106 n=20, 9 × 106 n=47, 2 × 107 n=47, or 1 × 108 PFU n=48) and 20 received placebo. Most adverse events occurred in the first day after vaccination, and were mild to moderate in intensity, of a short duration, and more frequent at high vaccine doses (9 × 106 PFU and greater). At the 2 × 107 PFU dose (used in phase 3 trials), the most common local adverse events versus placebo within the first 14 days were arm pain (57·4% 27 of 47 vs 7·4% seven of 94) and local tenderness (59·6% 28 of 47 vs 8·5% eight of 94). The most common systemic adverse events at the 2 × 107 PFU dose versus placebo, occurring in the first 14 days, were headache (46·8% 22 of 47 vs 27·7% 26 of 94), fatigue (38·3% 18 of 47 vs 19·1% 18 of 94), myalgia (34·0% 16 of 47 vs 10·6% 10 of 94), subjective fever (29·8% 14 of 47 vs 2·1% two of 94), shivering or chills (27·7% 13 of 47 vs 7·4% seven of 94), sweats (23·4% 11 of 47 vs 3·2% three of 94), joint aches and pain (19·1% nine of 47 vs 7·4% seven of 94), objective fever (14·9% seven of 47 vs 1·1% one of 94), and joint tenderness or swelling (14·9% seven of 47 vs 2·1% two of 94). Self-limited, post-vaccination arthritis occurred in 4·5% (19 of 418) of vaccinees (median onset 12·0 days IQR 10–14; median duration 8·0 days 6–15) versus 3·2% (three of 94) of controls (median onset 15·0 days 6–20; median duration 47·0 days 37–339), with no apparent dose relationship. Post-vaccination dermatitis occurred in 5·7% (24 of 418) of vaccinees (median onset 9·0 days IQR 2–12; median duration 7·0 days 4–9) versus 3·2% (three of 94) of controls (median onset 5·0 days 3–53; median duration 33·0 days 5–370). A low-level, transient, dose-dependent viraemia occurred in concert with early reactogenicity. Antibody responses were observed in most participants by day 14. IgG and neutralising antibody titres were dose-related (p=0·0003 for IgG ELISA and p<0·0001 for the 60% plaque-reduction neutralisation test PRNT60 by linear trend). On day 28 at the 2 × 107 PFU dose, the geometric mean IgG ELISA endpoint titre was 1624 (95% CI 1146–2302) and seroconversion was 95·7% (95% CI 85·5–98·8); the geometric mean neutralising antibody titre by PRNT60 was 250 (176–355) and seroconversion was 95·7% (85·5–98·8). These robust immunological responses were sustained for 1 year. Interpretation rVSV∆G-ZEBOV-GP was well tolerated and stimulated a rapid onset of binding and neutralising antibodies, which were maintained through to day 360. The immunogenicity results support selection of the 2 × 107 PFU dose. Funding Biomedical Advanced Research and Development Authority, US Department of Health and Human Services.
The 2008 discovery of an eruption of M31N 2008-12a began a journey on which the true nature of this remarkable recurrent nova continues to be revealed. M31N 2008-12a contains a white dwarf (WD) close ...to the Chandrasekhar limit, accreting at a high rate from its companion, and undergoes thermonuclear eruptions that are observed yearly and may even be twice as frequent. In this paper, we report on Hubble Space Telescope Space Telescope Imaging Spectrograph ultraviolet spectroscopy taken within days of the predicted 2015 eruption, coupled with Keck spectroscopy of the 2013 eruption. Together, this spectroscopy permits the reddening to be constrained to E ( B − V ) = 0.10 0.03 . The UV spectroscopy reveals evidence for highly ionized, structured, and high-velocity ejecta at early times. No evidence for neon is seen in these spectra, however, but it may be that little insight can be gained regarding the composition of the WD (CO versus ONe).
This meta-analysis aimed to compare conservative vs. operative treatment for humeral shaft fractures in terms of the nonunion rate, reintervention rate, permanent radial nerve palsy rate, and ...functional outcomes. Secondarily, effect estimates from observational studies were compared with estimates of randomized clinical trials (RCTs).
The PubMed/Medline, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched for both RCTs and observational studies comparing conservative with operative treatment for humeral shaft fractures.
A total of 2 RCTs (150 patients) and 10 observational studies (1262 patients) were included. The pooled nonunion rate of all studies was higher in patients treated conservatively (15.3%) vs. operatively (6.4%) (risk difference, 8%; odds ratio OR, 2.9; 95% confidence interval CI, 1.8-4.5; I2 = 0%). The reintervention rate was also higher for conservative treatment (14.3%) than for operative treatment (8.9%) (risk difference, 6%; OR, 1.9; 95% CI, 1.1-3.5; I2 = 30%). The higher reintervention rate was predominantly attributable to the higher nonunion rate in patients treated conservatively. The permanent radial nerve palsy rate was equal in both groups (OR, 0.6; 95% CI, 0.2-1.9; I2 = 18%). There appeared to be no difference in mean time to union and mean Disabilities of the Arm, Shoulder and Hand scores between the treatment groups. No difference was found between effect estimates form observational studies and RCTs.
This systematic review shows that satisfactory results can be achieved with both conservative and operative management; however, operative treatment reduces the risk of nonunion compared with conservative treatment, with comparable reintervention rates (for indications other than nonunion). Furthermore, operative treatment results in a similar permanent radial nerve palsy rate, despite its inherent additional surgery-related risks. No difference in mean time-to-union and short-term functional results was detected.
Background
Multiple rib fractures are associated with significant morbidity and mortality, especially in elderly patients. There is growing interest in surgical stabilization in this subgroup of ...patients. This systematic review compares conservative treatment to surgical fixation in elderly patients (older than 60 years) with multiple rib fractures. The primary outcome is mortality. Secondary outcomes include hospital and intensive care length of stay (HLOS and ILOS), duration of mechanical ventilation (DMV) and pneumonia rates.
Methods
Multiple databases were searched for comparative studies reporting on conservative versus operative treatment for rib fractures in patients older than 60 years. Both observational studies and randomised clinical trials were considered.
Results
Five observational studies (
n
= 2583) were included. Mortality was lower in operatively treated patients compared to conservative treatment (4% vs. 8%). Pneumonia rate and DMV were similar (5/6% and 5.8/6.5 days) for either treatment modality. Overall ILOS and HLOS of stay were longer in operatively treated patients (6.5 ILOS and 12.7 HLOS vs. 2.7 ILOS and 6.5 ILOS). There were only minimal reports on perioperative complications. Notably, the median number of rib fractures (8.4 vs. 5) and the percentage of flail chest were higher in operatively treated patients (47% vs. 39%).
Conclusion
It remains unknown to what extent conservative and operative treatment contribute individually to reducing morbidity and mortality in the elderly with multiple rib fractures. To date, the quality of evidence is rather low, thus well-performed comparative observational studies or randomised controlled trials considering all confounders are needed to determine whether operative treatment can improve a patient’s outcome.
To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody Rituxan (rituximab, IDEC-C2B8; Genentech Inc, South San Francisco, CA) and cyclophosphamide, doxorubicin, ...vincristine, and prednisone (CHOP) chemotherapy in patients with aggressive non-Hodgkin's lymphoma (NHL).
Thirty-three patients with previously untreated advanced aggressive B-cell NHL received six infusions of Rituxan (375 mg/m2 per dose) on day 1 of each cycle in combination with six doses of CHOP chemotherapy given on day 3 of each cycle.
The ORR by investigator assessment confirmed by the sponsor was 94% (31 of 33 patients). Twenty patients experienced a complete response (CR) (61%), 11 patients had a partial response (PR) (33%), and two patients were classified as having progressive disease. In the 18 patients with an International Prognostic Index (IPI) score > or = 2, the combination of Rituxan plus CHOP achieved an ORR of 89% and CR of 56%. The median duration of response and time to progression had not been reached after a median observation time of 26 months. Twenty-nine of 31 responding patients remained in remission during this follow-up period, including 15 of 16 patients with an IPI score > or = 2. The most frequent adverse events attributed to Rituxan were fever and chills, primarily during the first infusion. Rituxan did not seem to compromise the ability of patients to tolerate CHOP; all patients completed the entire six courses of the combination. The bcl-2 translocation of blood or bone marrow was positive at baseline in 13 patients; 11 patients had follow-up specimens obtained (eight CR, three PR), and all had a negative bcl-2 status after therapy. Only one patient has reconverted to bcl-2 positivity, and all patients remain in clinical remission.
This is the first report to demonstrate the safety and efficacy of the Rituxan chimeric anti-CD20 antibody in combination with standard-dose CHOP in the treatment of aggressive B-cell lymphoma. The clinical responses are at least comparable to those achieved with CHOP alone with no significant added toxicity. The presence or absence of the bcl-2 translocation did not affect the ability of patients to achieve a CR with this regimen. The ability to achieve sustained remissions in patients with an IPI score > or = 2 warrants further investigation with a randomized study.
To determine whether a response classification based on integration of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) into the International Workshop Criteria (IWC) provides a ...more accurate response assessment than IWC alone in patients with non-Hodgkin's lymphoma (NHL).
Fifty-four patients with aggressive NHL who underwent FDG-PET and computed tomography 1 to 16 weeks after four to eight cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone were assessed for complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD) by the IWC and by integrated IWC and FDG-PET (IWC+PET). Progression-free survival (PFS) was also compared between IWC- and IWC+PET-assigned response designations.
By IWC, 17 patients had a CR, seven had a CRu, 19 had a PR, nine had SD, and two had PD. In comparison, by IWC+PET, 35 patients had a CR, 12 had a PR, six had SD, one had PD, and zero had a CRu. In separate multivariate models, PFS was significantly shorter in patients with PR than in those with a CR using IWC (hazard ratio HR, 8.9; P = .021) or IWC+PET (HR, 29.7; P = .0003). However, when the two classifications were included in the same multivariate model, only IWC+PET was a statistically significant independent predictor for PFS (P = .008 v P = .72 for IWC). In addition, when patients with a PR by IWC and a CR by IWC+PET were compared with those with a CR by IWC and a CR by IWC+PET, there was no significant difference in PFS (HR, 1.6; P = .72), indicating that IWC+PET identified a subset of IWC-PR patients with a more favorable prognosis.
Compared with IWC, the IWC+PET-based assessment provides a more accurate response classification in patients with aggressive NHL.
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