Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 microg ethinyl estradiol and 3 mg drospirenone

BACKGROUND: The objective of this study was to compare cycle control, cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive (COC) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone. METHODS: A randomized, multicentre, open-label trial in which 983 women were treated (intent-to-treat population) with NuvaRing or the COC for 13 cycles. RESULTS: Breakthrough bleeding or spotting during cycles 2-13 was in general less frequent with NuvaRing than that with the COC (4.7-10.4%) and showed a statistically significant odds ratio of 0.61 (95% confidence interval: 0.46, 0.80) with longitudinal analysis. Intended bleeding was significantly better for all cycles with NuvaRing (55.2-68.5%) than that with the COC (35.6-56.6%) (P < 0.01). Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences. CONCLUSION: NuvaRing was associated with better cycle control than the COC, and there was no clinically relevant difference between the two groups in bodyweight.

Spectral biases in tree-ring climate proxies

External forcing and internal dynamics result in climate system variability ranging from sub-daily weather to multi-centennial trends and beyond1, 2. State-of-the-art palaeoclimatic methods routinely use hydroclimatic proxies to reconstruct temperature (for example, refs 3, 4), possibly blurring differences in the variability continuum of temperature and precipitation before the instrumental period. Here, we assess the spectral characteristics of temperature and precipitation fluctuations in observations, model simulations and proxy records across the globe. We find that whereas an ensemble of different general circulation models represents patterns captured in instrumental measurements, such as land–ocean contrasts and enhanced low-frequency tropical variability, the tree-ring-dominated proxy collection does not. The observed dominance of inter-annual precipitation fluctuations is not reflected in the annually resolved hydroclimatic proxy records. Likewise, temperature-sensitive proxies overestimate, on average, the ratio of low- to high-frequency variability. These spectral biases in the proxy records seem to propagate into multi-proxy climate reconstructions for which we observe an overestimation of low-frequency signals. Thus, a proper representation of the high- to low-frequency spectrum in proxy records is needed to reduce uncertainties in climate reconstruction efforts.

What are predictors for patients' quality of life after pelvic ring fractures?

Background Our knowledge of factors influencing mortality of patients with pelvic ring injuries and the impact of associated injuries is currently based on limited information. Questions/purposes Weidentified the (1) causes and time of death, (2) demography, and (3) pattern and severity of injuries in patients with pelvic ring fractures who did not survive. Methods We prospectively collected data on 5340 patients listed in the German Pelvic Trauma Registry between April 30, 2004 and July 29, 2011; 3034 of 5340 (57%) patientswere female. Demographic data and parameters indicating the type and severity of injury were recorded for patients who died in hospital (nonsurvivors) and compared with data of patients who survived (survivors). The median followup was 13 days (range, 0–1117 days). Results A total of 238 (4%) patients died a median of 2 days after trauma. The main cause of death was massive bleeding (34%), predominantly from the pelvic region (62% of all patients who died because of massive bleeding). Fifty six percent of nonsurvivors and 43% of survivors were male. Nonsurvivors were characterized by a higher incidence of complex pelvic injuries (32% versus 8%), less isolated pelvic ring fractures (13% versus 49%), lower initial blood hemoglobin concentration (6.7 ± 2.9 versus 9.8 ± 3.0 g/dL) and systolic arterial blood pressure (77 ± 27 versus 106 ± 24 mmHg), and higher injury severity score (ISS) (35 ± 16 versus 15 ± 12). Conclusion Patients with pelvic fractures who did not survive were characterized by male gender, severe multiple trauma, and major hemorrhage.

Acute and chronic pain in calves after different methods of rubber-ring castration

The goal of the present study was to evaluate the effect of different methods of rubber-ring castration on acute and chronic pain in calves. Sixty-three 4-6 week-old calves were randomly and sequentially allocated to one of five groups: Group RR (traditional rubber ring castration); group BRR (combination of one rubber ring with Burdizzo); group Rcut (one rubber ring applied with the scrotal tissue and rubber ring removed on day 9); group 3RR (three rubber rings placed one above the other around the scrotal neck); and group CO (controls; sham-castrated). All calves received 0.2 mL/kg bodyweight lidocaine 2%, injected into the spermatic cords and around the scrotal neck 15 min before castration. The presence of acute and chronic pain was assessed using plasma cortisol concentrations, response to palpation of scrotal area, time from castration until complete wound healing, and behavioural signs. Calves of group 3RR showed severe swelling and inflammation, and licking of the scrotal area occurred significantly more often than in groups Rcut and CO. Technique 3RR was discontinued for welfare reasons before the end of the study. All castration groups had significantly more pain upon palpation than calves of group CO, but palpation elicited markedly less pain in group Rcut than in the other castration groups. The most rapid healing time and shortest duration of chronic pain after castration was achieved in group Rcut. For welfare reasons, the Rcut technique should be considered as a valuable alternative to traditional rubber ring castration of calves at 4-6 weeks of age.

Chemistry of pyrrocorphins: synthesis of isobacteriochlorins and pyrrocorphins bearing a methyl group at the meso position between rings A and D

A sigmatropic methyl shift from the angular position C-1 in ring to the position C-20 between rings and constitutes the crucial step in syntheses leading to a 20-methyl-isobacteriochlorin and to 20-methyl-pyrrocorphins which served as substrates in the investigation presented in the accompanying communication.

The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola

A World Health Organization expert meeting on Ebola vaccines proposed urgent safety and efficacy studies in response to the outbreak in West Africa. One approach to communicable disease control is ring vaccination of individuals at high risk of infection due to their social or geographical connection to a known case. This paper describes the protocol for a novel cluster randomised controlled trial design which uses ring vaccination.In the Ebola ça suffit ring vaccination trial, rings are randomised 1:1 to (a) immediate vaccination of eligible adults with single dose vaccination or (b) vaccination delayed by 21 days. Vaccine efficacy against disease is assessed in participants over equivalent periods from the day of randomisation. Secondary objectives include vaccine effectiveness at the level of the ring, and incidence of serious adverse events.Ring vaccination trials are adaptive, can be run until disease elimination, allow interim analysis, and can go dormant during inter-epidemic periods.

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.

Giant Electric Field Enhancement in Split Ring Resonators Featuring Nanometer-Sized Gaps

Today's pulsed THz sources enable us to excite, probe, and coherently control the vibrational or rotational dynamics of organic and inorganic materials on ultrafast time scales. Driven by standard laser sources THz electric field strengths of up to several MVm−1 have been reported and in order to reach even higher electric field strengths the use of dedicated electric field enhancement structures has been proposed. Here, we demonstrate resonant electric field enhancement structures, which concentrate the incident electric field in sub-diffraction size volumes and show an electric field enhancement as high as ~14,000 at 50 GHz. These values have been confirmed through a combination of near-field imaging experiments and electromagnetic simulations.

[Influence of the pelvic trauma registry of the DGU on treatment of pelvic ring fractures].

Fractures of the pelvic ring are comparatively rare with an incidence of 2-8 % of all fractures depending on the study in question. The severity of pelvic ring fractures can be very different ranging from simple and mostly "harmless" type A fractures up to life-threatening complex type C fractures. Although it was previously postulated that high-energy trauma was necessary to induce a pelvic ring fracture, over the past decades it became more and more evident, not least from data in the pelvic trauma registry of the German Society for Trauma Surgery (DGU), that low-energy minor trauma can also cause pelvic ring fractures of osteoporotic bone and in a rapidly increasing population of geriatric patients insufficiency fractures of the pelvic ring are nowadays observed with no preceding trauma.Even in large trauma centers the number of patients with pelvic ring fractures is mostly insufficient to perform valid and sufficiently powerful monocentric studies on epidemiological, diagnostic or therapeutic issues. For this reason, in 1991 the first and still the only registry worldwide for the documentation and evaluation of pelvic ring fractures was introduced by the Working Group Pelvis (AG Becken) of the DGU. Originally, the main objectives of the documentation were epidemiological and diagnostic issues; however, in the course of time it developed into an increasingly expanding dataset with comprehensive parameters on injury patterns, operative and conservative therapy regimens and short-term and long-term outcome of patients. Originally starting with 10 institutions, in the meantime more than 30 hospitals in Germany and other European countries participate in the documentation of data. In the third phase of the registry alone, which was started in 2004, data from approximately 15,000 patients with pelvic ring and acetabular fractures were documented. In addition to the scientific impact of the pelvic trauma registry, which is reflected in the numerous national and international publications, the dramatically changing epidemiology of pelvic ring fractures, further developments in diagnostics and the changes in operative procedures over time could be demonstrated. Last but not least the now well-established diagnostic and therapeutic algorithms for pelvic ring fractures, which could be derived from the information collated in registry studies, reflect the clinical impact of the registry.