A Neutralizing Monoclonal Antibody Targeting the Acid-Sensitive Region in Chikungunya Virus E2 Protects from Disease.

The mosquito-borne alphavirus, chikungunya virus (CHIKV), has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute and chronic rheumatic disease. There are currently no licensed vaccines for CHIKV and current anti-inflammatory drug treatment is often inadequate. Here we describe the isolation and characterization of two human monoclonal antibodies, C9 and E8, from CHIKV infected and recovered individuals. C9 was determined to be a potent virus neutralizing antibody and a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 and E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR) of the CHIKV E2 glycoprotein. The ASR is critical for the rearrangement of CHIKV E2 during fusion and viral entry into host cells, and we predict that C9 prevents these events from occurring. When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia and arthritis. We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model. Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro and in vivo, it is likely to be an important region both for future antibody and vaccine-based interventions against CHIKV

Municipal mortality due to thyroid cancer in Spain

BACKGROUND: Thyroid cancer is a tumor with a low but growing incidence in Spain. This study sought to depict its spatial municipal mortality pattern, using the classic model proposed by Besag, York and Mollié. METHODS: It was possible to compile and ascertain the posterior distribution of relative risk on the basis of a single Bayesian spatial model covering all of Spain's 8077 municipal areas. Maps were plotted depicting standardized mortality ratios, smoothed relative risk (RR) estimates, and the posterior probability that RR > 1. RESULTS: From 1989 to 1998 a total of 2,538 thyroid cancer deaths were registered in 1,041 municipalities. The highest relative risks were mostly situated in the Canary Islands, the province of Lugo, the east of La Coruña (Corunna) and western areas of Asturias and Orense. CONCLUSION: The observed mortality pattern coincides with areas in Spain where goiter has been declared endemic. The higher frequency in these same areas of undifferentiated, more aggressive carcinomas could be reflected in the mortality figures. Other unknown genetic or environmental factors could also play a role in the etiology of this tumor

Spatial and temporal facies evolution of a Lower Jurassic carbonate platform, NW Tethyan margin (Mallorca, Spain)

The variety of depositional facies of a Lower Jurassic carbonate platform has been investigated on the island of Mallorca along a transect comprising six stratigraphic profiles. Twenty-nine facies and sub-facies have been recognized, grouped into seven facies associations, ranging in depositional environment from supratidal/terrestrial and peritidal to outer platform. Spatial and temporal (2D) facies distribution along the transect reflects the evolution of the carbonate platform with time showing different facies associations, from a broad peritidal platform (stage 1) to a muddy open platform (stage 2), and finally to a peritidal to outer carbonate platform (stage 3). Stage 1 (early Sinemurian to earliest late Sinemurian) corresponds to a nearly-flat peritidal-shallow subtidal epicontinental platform with facies belts that shifted far and fast over the whole study area. The evolution from stage 1 to stage 2 (late Sinemurian) represents a rapid flooding of the epicontinental shallow platform, with more open-marine conditions, and the onset of differential subsidence. During stage 3 (latest Sinemurian), peritidal and shallow-platform environments preferentially developed to the northeast (Llevant Mountains domain) with a rapid transition to middle-outer platform environments toward the northwest (Tramuntana Range domain). Stages 1 and 3 present facies associations typical of Bahamian-type carbonates, whereas stage 2 represents the demise of the Bahamian-type carbonate factory and proliferation of muddy substrates with suspension-feeders. The described platform evolution responded to the interplay between the initial extensional tectonic phases related to Early Jurassic Tethyan rifting, contemporaneous environmental perturbations, and progressive platform flooding related to the Late Triassic–Early Jurassic worldwide marine transgression and associated accommodation changes

Detection chain and electronic readout of the QUBIC instrument

The Q and U Bolometric Interferometer for Cosmology (QUBIC) Technical Demonstrator (TD) aiming to shows the feasibility of the combination of interferometry and bolometric detection. The electronic readout system is based on an array of 128 NbSi Transition Edge Sensors cooled at 350mK readout with 128 SQUIDs at 1K controlled and amplified by an Application Specific Integrated Circuit at 40K. This readout design allows a 128:1 Time Domain Multiplexing. We report the design and the performance of the detection chain in this paper. The technological demonstrator unwent a campaign of test in the lab. Evaluation of the QUBIC bolometers and readout electronics includes the measurement of I-V curves, time constant and the Noise Equivalent Power. Currently the mean Noise Equivalent Power is ~ 2 x 10⁻¹⁶ W/√Hz

Detection chain and electronic readout of the QUBIC instrument

The Q and U Bolometric Interferometer for Cosmology (QUBIC) Technical Demonstrator (TD) aiming to shows the feasibility of the combination of interferometry and bolometric detection. The electronic readout system is based on an array of 128 NbSi Transition Edge Sensors cooled at 350mK readout with 128 SQUIDs at 1K controlled and amplified by an Application Specific Integrated Circuit at 40K. This readout design allows a 128:1 Time Domain Multiplexing. We report the design and the performance of the detection chain in this paper. The technological demonstrator unwent a campaign of test in the lab. Evaluation of the QUBIC bolometers and readout electronics includes the measurement of I-V curves, time constant and the Noise Equivalent Power. Currently the mean Noise Equivalent Power is ~ 2 x 10⁻¹⁶ W/√Hz

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research