Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial.

BACKGROUND A recombinant, replication-competent vesicular stomatitis virus-based vaccine expressing a surface glycoprotein of Zaire Ebolavirus (rVSV-ZEBOV) is a promising Ebola vaccine candidate. We report the results of an interim analysis of a trial of rVSV-ZEBOV in Guinea, west Africa. METHODS For this open-label, cluster-randomised ring vaccination trial, suspected cases of Ebola virus disease in Basse-Guinée (Guinea, west Africa) were independently ascertained by Ebola response teams as part of a national surveillance system. After laboratory confirmation of a new case, clusters of all contacts and contacts of contacts were defined and randomly allocated 1:1 to immediate vaccination or delayed (21 days later) vaccination with rVSV-ZEBOV (one dose of 2 × 10(7) plaque-forming units, administered intramuscularly in the deltoid muscle). Adults (age ≥18 years) who were not pregnant or breastfeeding were eligible for vaccination. Block randomisation was used, with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 vs >20 individuals). The study is open label and masking of participants and field teams to the time of vaccination is not possible, but Ebola response teams and laboratory workers were unaware of allocation to immediate or delayed vaccination. Taking into account the incubation period of the virus of about 10 days, the prespecified primary outcome was laboratory-confirmed Ebola virus disease with onset of symptoms at least 10 days after randomisation. The primary analysis was per protocol and compared the incidence of Ebola virus disease in eligible and vaccinated individuals in immediate vaccination clusters with the incidence in eligible individuals in delayed vaccination clusters. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. FINDINGS Between April 1, 2015, and July 20, 2015, 90 clusters, with a total population of 7651 people were included in the planned interim analysis. 48 of these clusters (4123 people) were randomly assigned to immediate vaccination with rVSV-ZEBOV, and 42 clusters (3528 people) were randomly assigned to delayed vaccination with rVSV-ZEBOV. In the immediate vaccination group, there were no cases of Ebola virus disease with symptom onset at least 10 days after randomisation, whereas in the delayed vaccination group there were 16 cases of Ebola virus disease from seven clusters, showing a vaccine efficacy of 100% (95% CI 74·7-100·0; p=0·0036). No new cases of Ebola virus disease were diagnosed in vaccinees from the immediate or delayed groups from 6 days post-vaccination. At the cluster level, with the inclusion of all eligible adults, vaccine effectiveness was 75·1% (95% CI -7·1 to 94·2; p=0·1791), and 76·3% (95% CI -15·5 to 95·1; p=0·3351) with the inclusion of everyone (eligible or not eligible for vaccination). 43 serious adverse events were reported; one serious adverse event was judged to be causally related to vaccination (a febrile episode in a vaccinated participant, which resolved without sequelae). Assessment of serious adverse events is ongoing. INTERPRETATION The results of this interim analysis indicate that rVSV-ZEBOV might be highly efficacious and safe in preventing Ebola virus disease, and is most likely effective at the population level when delivered during an Ebola virus disease outbreak via a ring vaccination strategy. FUNDING WHO, with support from the Wellcome Trust (UK); Médecins Sans Frontières; the Norwegian Ministry of Foreign Affairs through the Research Council of Norway; and the Canadian Government through the Public Health Agency of Canada, Canadian Institutes of Health Research, International Development Research Centre, and Department of Foreign Affairs, Trade and Development.

SMARTnet: First Experience of Setting Up a Telescope System to Survey the Geostationary Ring

Space debris in geostationary orbits may be detected with optical telescopes when the objects are illuminated by the Sun. The advantage compared to Radar can be found in the illumination: radar illuminates the objects and thus the detection sensitivity depletest proportional to the fourth power of the d istance. The German Space Operation Center, GSOC, together with the Astronomical Institute of the University of Bern, AIUB, are setting up a telescope system called SMARTnet to demonstrate the capability of performing geostationary surveillance. Such a telescope system will consist of two telescopes on one mount: a smaller telescope with an aperture of 20cm will serve for fast survey while the larger one, a telescope with an aperture of 50cm, will be used for follow-up observations. The telescopes will be operated by GSOC from Oberpfaffenhofen by the internal monitoring and control system called SMARTnetMAC. The observation plan will be generated by MARTnetPlanning seven days in advance by applying an optimized planning scheduler, taking into account fault time like cloudy nights, priority of objects etc. From each picture taken, stars will be identified and everything not being a star is treated as a possible object. If the same object can be identified on multiple pictures within a short time span, the trace is called a tracklet. In the next step, several tracklets will be correlated to identify individual objects, ephemeris data for these objects are generated and catalogued . This will allow for services like collision avoidance to ensure safe operations for GSOC’s satellites. The complete data processing chain is handled by BACARDI, the backbone catalogue of relational debris information and is presented as a poster.

Gas-phase fragmentation and conformation of the sugar-modified antisense oligonucleotide tcDNA

Tricyclo-DNA (tcDNA) is a sugar- and backbone-modified analogue of DNA that is currently tested as antisense oligonucleotide for the treatment of Duchenne muscular dystrophy. The name tricyclo-DNA is derived from the modified sugar-moiety: the deoxyribose is extended to a three-membered ring system. This modification is designed to limit the flexibility of the structure, thus giving rise to entropically stabilized hybrid duplexes formed between tcDNA and complementary DNA or RNA oligonucleotides. While the structural modifications increase the biostability of the therapeutic agent, they also render the oligonucleotide inaccessible to enzyme-based sequencing methods. Tandem mass spectrometry constitutes an alternative sequencing technique for partially and fully modified oligonucleotides. For reliable sequencing, the fragmentation mechanism of the structure in question must be understood. Therefore, the presented work evaluates the effect of the modified sugar-moiety on the gas-phase dissociation of single stranded tcDNA. Moreover, our experiments reflect the exceptional gas-phase stability of hybrid duplexes that is most noticeable in the formation of truncated duplex ions upon collision-induced dissociation. The stability of the duplex arises from the modified sugar-moiety, as the rigid structure of the tcDNA single strand minimizes the change of the entropy for the annealing. Moreover, the tc-modification gives rise to extended conformations of the nucleic acids in the gas-phase, which was studied by ion mobility spectrometry-mass spectrometry.

Anterior fixation of unstable pelvic ring fractures using the modified Stoppa approach: mid-term results are independent on patients' age

PURPOSE Open surgical management of unstable pelvic ring injuries has been discussed controversially compared to percutaneous techniques in terms of surgical site morbidity especially in older patients. Thus, we assessed the impact of age on the outcome following fixation of unstable pelvic ring injuries through the modified Stoppa approach. METHODS Out of a consecutive series of 92 patients eligible for the study, 63 patients (mean age 50 years, range 19-78) were evaluated [accuracy of reduction, complications, failures, Majeed-Score, Oswestry Disability Questionnaire (ODI), Mainz Pain Staging System (MPSS)] at a mean follow-up of 3.3 years (range 1.0-7.9). Logistic multivariate regression analysis was performed to assess the outcome in relation to increasing patient age and/or Injury Severity Score (ISS). RESULTS Out of 63 patients, in 36 an "anatomic" reduction was achieved. Ten postoperative complications occurred in eight patients. In five patients, failure of fixation was noted at the anterior and/or posterior pelvic ring. In 49 patients, an "excellent" or "good" Majeed-Score was obtained; the mean ODI was 14 % (range 0-76 %); 50 patients reported either no or only minor chronic pelvic pain (MPSS). Only an increasing ISS conferred an increased likelihood of the occurrence of a non-anatomical reduction, a "poor" or "fair" Majeed-Score, or an ODI >20 %. CONCLUSIONS Increasing age did not impact the analysed parameters. Open reduction and internal fixation of the anterior pelvic ring through a modified Stoppa approach in unstable pelvic ring injuries did not result in an unfavourable outcome with increasing age of patients.

Assessment of the Breakaway Torque at the Posterior Pelvic Ring in Human Cadavers

PURPOSE To enhance the diminished screw purchase in cancellous, osteoporotic bone following the fixation of posterior pelvic ring injuries by iliosacral screws an increased bone-implant contact area using modificated screws, techniques or bone cement may become necessary. The aim of the study was to identify sites within the pathway of iliosacral screws requiring modifications of the local bone or the design of instrumentations placed at this site. MATERIALS AND METHODS The breakaway torque was measured mechanically at the iliosacral joint ("ISJ"), the sacral lateral mass ("SLM") and the center of the S1 ("CS1"), at a superior and an inferior site under fluoroscopic control on five human cadaveric specimens (3 female; mean age 87 years, range: 76-99) using the DensiProbe™Spine device. RESULTS The measured median (range) breakaway torque was 0.63 Nm (0.31-2.52) at the "iliosacral joint", 0.14 Nm (0.05-1.22) at the "sacral lateral mass", 0.57 Nm (0.05-1.42) at the "S1 center." The "sacral lateral mass" breakaway torque was lower than compared to that at the "iliosacral joint" (p < .001) or "S1 center" (p < .001). The median (range) breakaway torque measured at all superior measurement points was 0.52 Nm (0.10-2.52), and 0.48 Nm (0.05-1.18) at all inferior sites. The observed difference was statistically significant (p < .05). CONCLUSIONS The lateral mass of the sacrum provides the lowest bone quality for implant anchorage. Iliosacral screws should be placed as superior as safely possible, should bridge the iliosacral joint and may allow for cement application at the lateral mass of the sacrum through perforations.

A cross-sectional analysis of the association between polycyclic aromatic hydrocarbons and diesel particulate matter exposures and hypertension among individuals of Mexican origin residing in Houston, TX

Background. Research has shown that elevations of only 10 mmHg diastolic blood pressure (BP) and 5 mmHg systolic BP are associated with substantial (as large as 50%) increases in risks for cardiovascular disease, a leading cause of death, worldwide. Epidemiological studies have found that particulate matter (PM) increases blood pressure (BP) and many biological mechanisms which may suggest that the organic matter of PM contributes to the increase in BP. To understand components of PM which may contribute to the increase in BP, this study focuses on diesel particulate matter (DPM) and polycyclic aromatic hydrocarbons (PAHs). To our knowledge, there have been only four epidemiological studies on BP and DPM, and no epidemiological studies on BP and PAHs. ^ Objective. Our objective was to evaluate the association between prevalent hypertension and two ambient exposures: DPM and PAHs amongst the Mano a Mano cohort. ^ Methods. The Mano a Mano cohort which was established by the M.D. Anderson Cancer Center in 2001, is comprised of individuals of Mexican origin residing in Houston, TX. Using geographical information systems, we linked modeled annual estimates of PAHs and DPM at the census track level from the U.S. Environmental Protection Agency's National-Scale Air Toxics Assessment to residential addresses of cohort members. Mixed-effects logistic regression models were applied to determine associations between DPM and PAHs and hypertension while adjusting for confounders. ^ Results. Ambient levels of DPM, categorized into quartiles, were not statistically associated with hypertension and did not indicate a dose response relationship. Ambient levels of PAHs, categorized into quartiles, were not associated with hypertension, but did indicate a dose response relationship in multiple models (for example: Q2: OR = 0.98; 95% CI, 0.73–1.31, Q3: OR = 1.08; 95% CI, 0.82–1.41, Q4: OR = 1.26; 95% CI, 0.94–1.70). ^ Conclusion. This is the first assessment to analyze the relationship between ambient levels of PAHs and hypertension and it is amongst a few studies investigating the association between ambient levels of DPM and hypertension. Future analyses are warranted to explore the effects DPM and PAHs using different categorizations in order to clarify their relationships with hypertension.^

Lipids and polycyclic aromatic hydrocarbons in bottom sediments from the Atlantic sector of the Southern Ocean

Distribution and composition of lipids and contents of alkanes and polycyclic aromatic hydrocarbons(PAHs) in bottom sediments of the Scotia and Weddell seas are discussed. Comparatively low concentrations of organic carbon (average 0.35%) and lipids (average 0.024%) result from rapid decomposition of organic matter in upper layers of the water column. Composition of alkanes indicates that lipids are of autochthonous origin, and stable concentrations of PAHs (average 25.8 ppb, sigma 15.3 ppb) indicate that they represent the background level for bottom sediments. Higher concentrations of PAHs in sediments near the King George Island (252.1 ppb) and different distributions of individual polyarenes are produced there by the heating systems of the Polish Antarctic Station.

Distribution of polycyclic aromatic hydrocarbons in eolian and eolian-deluvial sediments from the North Iceland

This work considers results of a study of Holocene cover sediments in Iceland. They are largely composed of wind-transported palagonitized hyaloclastite particles and coeval horizons of acid and basic tephras. It is established that polyciclic aromatic hydrocarbons (PAH) are released from basaltic glass in natural environments only in case of intense physicochemical alteration and destruction of its structure. This process does not influence PAH composition and their quantitative proportions. No new PAH formed during several thousands of years in Holocene section. Hydrocarbons are transferred from fixed state in basaltic glass into free state in palagonites practically without any changes. PAH were mainly redeposited by winds, derived together with palagonite from weathered hyaloclastites, and precipitated from atmosphere with tephra during eruptions.