Nanoantenna-enhanced ultrafast nonlinear spectroscopy of a single gold nanoparticle

Optical nanoantennas are a novel tool to investigate previously unattainable dimensions in the nanocosmos. Just like their radio-frequency equivalents, nanoantennas enhance the light-matter interaction in their feed gap. Antenna enhancement of small signals promises to open a new regime in linear and nonlinear spectroscopy on the nanoscale. Without antennas especially the nonlinear spectroscopy of single nanoobjects is very demanding. Here, we present for the first time antenna-enhanced ultrafast nonlinear optical spectroscopy. In particular, we utilize the antenna to determine the nonlinear transient absorption signal of a single gold nanoparticle caused by mechanical breathing oscillations. We increase the signal amplitude by an order of magnitude which is in good agreement with our analytical and numerical models. Our method will find applications in linear and nonlinear spectroscopy of nanoobjects, ranging from single protein binding events via nonlinear tensor elements to the limits of continuum mechanics

Ultrasound imaging for identification of cerebral damage in congenital Zika virus syndrome: a case series.

Zika virus is a novel teratogenic agent associated with cerebral anomalies. Because of the challenges associated with assessment of antenatal diagnosis and prognosis in fetuses, screening for other congenital infections mostly relies on ultrasound. We aimed to assess whether a similar approach might be adequate for Zika virus congenital syndrome provided that early markers of infection and adequate timing for screening are established. For this case series we reviewed all pregnant women who had a laboratory-confirmed Zika virus infection in their first trimester or early second trimester and abnormal fetal ultrasound findings who were managed at the Pluridisciplinary Center for Prenatal Diagnosis of Martinique during the Zika virus epidemic (Jan 1, 2016, to Nov 10, 2016) in Martinique, a French Caribbean island. Ultrasound imaging was done with GE Healthcare Voluson E10 and E8 machines with abdominal and vaginal probes. We analysed 14 cases of pregnant women with confirmed Zika virus infection and fetal abnormalities of the brain, and 31 ultrasound imaging results. Between 16 and 20 weeks of gestation, four (33%) of 12 fetuses had an abnormal ultrasound examination. Anomalies were detected in nine (90%) of the ten fetuses from whom ultrasound images were obtained between 20 and 24 weeks of gestation. All five remaining fetuses at 24-28 weeks of gestation, and all four after 28 weeks, had severe anomalies. Major anomalies identified were ventriculomegaly (12 fetuses, 86%), cortical atrophy (11, 79%), calcifications (ten, 71%; particularly located at the corticosubcortical junction), and anomalies of the corpus callosum (ten, 71%). Prenatal assessment of head circumference measurement by imaging was not an effective screening tool for congenital Zika virus infection, with microcephaly only identified in nine (64%) fetuses. Ultrasound monitoring appears to be a good screening strategy to monitor Zika virus-exposed pregnancies. Public health efforts should focus on scanning at 22-26 weeks of gestation. Identification of ventriculomegaly, cortical atrophy, calcifications, and anomalies of the corpus callosum should prompt laboratory screening for Zika virus. None

Our Forage Resources

[Contents:] Relative Values of Forage, Food, and Other Crop Products -- The Development of Forage Production -- Relations between Livestock and Human Population -- Relations Between Livestock and Forage Production -- Forage Production in the Different Agricultural Regions -- Harvested Forage -- Classes of Harvested Forage -- The Principal Forage-Producing Crops -- Pasturage -- Area and Carrying Capacity of Certain Classes of Grazing Land -- Terms Relating to Pastures -- Systems of Grazing -- Kinds of Pasture -- The Pasture Regions -- Improvement of Methods in the Western Range Region -- Control of Grazing Lands in the Western Range Region -- Economic Importance of Farm Pastures -- Value of Pastures in the United States -- Bulletins Relating to Hay, Fodder, and Pasture

Our Forage Resources

[Contents:] Relative Values of Forage, Food, and Other Crop Products -- The Development of Forage Production -- Relations between Livestock and Human Population -- Relations Between Livestock and Forage Production -- Forage Production in the Different Agricultural Regions -- Harvested Forage -- Classes of Harvested Forage -- The Principal Forage-Producing Crops -- Pasturage -- Area and Carrying Capacity of Certain Classes of Grazing Land -- Terms Relating to Pastures -- Systems of Grazing -- Kinds of Pasture -- The Pasture Regions -- Improvement of Methods in the Western Range Region -- Control of Grazing Lands in the Western Range Region -- Economic Importance of Farm Pastures -- Value of Pastures in the United States -- Bulletins Relating to Hay, Fodder, and Pasture

Baricitinib in juvenile idiopathic arthritis: an international, phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial

Background Juvenile idiopathic arthritis can be refractory to some or all treatment regimens, therefore new medications are needed to treat this population. This trial assessed the efficacy and safety of baricitinib, an oral Janus kinase 1/2-selective inhibitor, versus placebo in patients with juvenile idiopathic arthritis.Methods This phase 3, randomised, double-blind, placebo-controlled, withdrawal, efficacy, and safety trial was conducted in 75 centres in 20 countries. We enrolled patients (aged 2 to <18 years) with polyarticular juvenile idiopathic arthritis (positive or negative for rheumatoid factor), extended oligoarticular juvenile idiopathic arthritis, enthesitis- related arthritis, or juvenile psoriatic arthritis, and an inadequate response (after =12 weeks of treatment) or intolerance to one or more conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). The trial consisted of a 2-week safety and pharmacokinetic period, a 12-week open-label lead-in period (10 weeks for the safety and pharmacokinetic subcohort), and an up to 32-week placebo-controlled double-blind withdrawal period. After age- based dosing was established in the safety and pharmacokinetic period, patients received a once-daily 4 mg adult- equivalent dose of baricitinib (tablets or suspension) in the open-label lead-in period. Patients meeting Juvenile Idiopathic Arthritis-American College of Rheumatology (JIA-ACR) 30 criteria (JIA-ACR30 responders) at the end of the open-label lead-in (week 12) were eligible for random assignment (1:1) to receive placebo or continue receiving baricitinib, and remained in the double-blind withdrawal period until disease flare or up to the end of the double-blind withdrawal period (week 44). Patients and any personnel interacting directly with patients or sites were masked to group assignment. The primary endpoint was time to disease flare during the double-blind withdrawal period and was assessed in the intention-to-treat population of all randomly assigned patients. Safety was assessed in all patients who received at least one dose of baricitinib throughout the three trial periods. For adverse events in the double-blind withdrawal period, exposure-adjusted incidence rates were calculated. The trial was registered on ClinicalTrials.gov, NCT03773978, and is completed.Findings Between Dec 17, 2018 and March 3, 2021, 220 patients were enrolled and received at least one dose of baricitinib (152 [69%] girls and 68 [31%] boys; median age 14.0 years [IQR 12.0-16.0]). 219 patients received baricitinib in the open-label lead-in period, of whom 163 (74%) had at least a JIA-ACR30 response at week 12 and were randomly assigned to placebo (n=81) or baricitinib (n=82) in the double-blind withdrawal period. Time to disease flare was significantly shorter with placebo versus baricitinib (hazard ratio 0.241 [95% CI 0.128-0.453], p<0.0001). Median time to flare was 27.14 weeks (95% CI 15.29-not estimable) in the placebo group, and not evaluable for patients in the baricitinib group (<50% had a flare event). Six (3%) of 220 patients had serious adverse events during the safety and pharmacokinetic period or open-label lead-in period. In the double-blind withdrawal period, serious adverse events were reported in four (5%) of 82 patients (incidence rate [IR] 9.7 [95% CI 2.7-24.9] per 100 patient-years at risk) in the baricitinib group and three (4%) of 81 (IR 10.2 [2.1-29.7]) in the placebo group.Treatment-emergent infections were reported during the safety and pharmacokinetic or open-label lead-in period in 55 (25%) of 220 patients, and during the double-blind withdrawal period in 31 (38%) of 82 (IR 102.1 [95% CI 69.3-144.9]) in the baricitinib group and 15 (19%) of 81 (IR 59.0 [33.0-97.3]) in the placebo group. Pulmonary embolism was reported as a serious adverse event in one patient (1%; IR 2.4 [95% CI 0.1-13.3]) in the baricitinib group in the double-blind withdrawal period, which was judged to be related to study treatment.Interpretation Baricitinib was efficacious with an acceptable safety profile in the treatment of polyarticular juvenile idiopathic arthritis, extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, and juvenile psoriatic arthritis, after inadequate response or intolerance to standard therapy

A Comparison of Random Task Graph Generation Methods for Scheduling Problems

International audienceHow to generate instances with relevant properties and without bias remains an open problem of critical importance to compare heuristics fairly. When scheduling with precedence constraints, the instance is a task graph that determines a partial order on task executions. To avoid selecting instances among a set populated mainly with trivial ones, we rely on properties such as the mass, which measures how much a task graph can be decomposed into smaller ones. This property and an in-depth analysis of existing random instance generators establish the sub-exponential generic time complexity of the studied problem