Summary Background Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in children. We aimed to assess the safety and efficacy of an anti-RSV monoclonal ...antibody (motavizumab) in healthy term (≥36 weeks' gestational age) infants for the prevention of medically attended RSV acute lower respiratory tract infections. Methods This phase 3, double-blind, placebo-controlled, randomised trial enrolled healthy Native American infants aged 6 months or younger who were born at 36 weeks' gestational age in southwestern USA, on the Navajo Nation, the White Mountain Apache reservation, and the San Carlos Apache Indian reservation. Participants were randomly assigned (2:1) to receive either five monthly intramuscular doses of motavizumab (15 mg/kg) or placebo. They were followed up for 150 days after the first dose, and the primary endpoints were respiratory admission to hospital with a positive result for RSV by RT-PCR and death caused by RSV. Participants were followed up for medically attended wheezing until they reached age 3 years. Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov , number NCT00121108. Findings During the autumn seasons (October to December) between 2004 and 2007, 2127 infants of the 2596 infants enrolled were randomly assigned to receive either motavizumab (1417) or placebo (710). After ITT analysis, motavizumab resulted in an 87% relative reduction (relative risk RR 0·13, 95% CI 0·08–0·21) in the proportion of infants admitted to hospital with RSV (21 2% of 1417 participants who received motavizumab; 80 11% of 710 participants who received placebo, p<0·0001). Serious adverse events were less common in particpants taking motavizumab (212 15%) than particpants on placebo (148 21%). Six deaths occurred in study participants (motavizumab, n=4 0·3%; placebo, n=2 0·3%); none were deemed to be related to the study product. Hypersensitivity events were more common in patients given motavizumab (208 14·7%) than in placebo recipients (87 12·3%; p=0·14). There was no effect on rates of medically attended wheezing in children aged 1–3 years (190 14·9% of participants randomly assigned to receive motavizumab vs 90 14·0% participants randomly assigned to receive placebo). Interpretation To our knowledge, this is the only trial of an anti-RSV antibody to prevent serious RSV disease in healthy term infants. Motavizumab significantly reduced the RSV-associated inpatient and outpatient burden and set a benchmark for the efficacy of RSV prevention strategies. The findings do not support a direct, generalisable, causal association between RSV lower respiratory tract infection and subsequent long-term wheezing in term infants. Funding MedImmune.
In this trial in patients with relapsed CLL, progression-free survival at 2 years was 78% with zanubrutinib and 66% with ibrutinib. Infections were common with both; cardiac events were less frequent ...with zanubrutinib.
Summary Background Ibrutinib, an orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK), is an effective treatment for relapsed chronic lymphocytic leukaemia (CLL). We investigated ...the activity and safety of the combination of ibrutinib with the monoclonal antibody rituximab in patients with high-risk CLL. Methods In this single-arm phase 2 study, we enrolled adult patients with high-risk CLL at the MD Anderson Cancer Center (Houston, TX, USA). All enrolled participants had high-risk cytogenetic abnormalities (deletion 17p, TP53 mutation, or deletion 11q) or a short progression-free survival (PFS <36 months) after previous first-line chemoimmunotherapy. Patients with symptomatic disease requiring therapy received 28-day cycles of once-daily ibrutinib 420 mg together with rituximab (375 mg/m2 , intravenously, every week during cycle 1, then once per cycle until cycle 6), followed by continuous daily single-agent ibrutinib 420 mg until disease progression or until toxicities or complications precluded further treatment. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov number NCT01520519 , and is no longer accruing patients. Findings Between Feb 28, 2012, and Sept 11, 2012, we enrolled 40 patients with CLL with high-risk disease features, 20 of whom had deletion 17p (del17p) or TP53 mutations (16 previously treated, four untreated), 13 had relapsed CLL with deletion 11q (del11q), and seven a PFS less than 36 months after first-line chemoimmunotherapy. 18-month PFS in all patients was 78·0% (95% CI 60·6–88·5), whereas in those with a del(17p) or TP53 mutation it was 72·4% (45·6–87·6) Toxicity was mainly mild to moderate in severity (grade 1–2). Diarrhoea occurred in ten (25%) patients (grade 1 in nine patients and grade 2 in one), bleeding events in 14 (33%) patients (eight grade 1 and five grade 2), nausea or vomiting in 15 patients (38%) (ten grade 1 and five grade 2), and fatigue in seven (18%) patients (four grade 1 and three grade 2). Five patients (13%) had grade 3 infections (two lung infections, one upper respiratory tract infection, one sepsis, and one mucositis), and no grade 4 or 5 infections occurred. One patient had grade 4 neutropenia. Interpretation The encouraging safety and activity of ibrutinib and rituximab in this population of patients with high-risk CLL merits further investigation of this combination. Funding Pharmacyclics Inc, Cancer Prevention and Research Institute of Texas, Leukemia and Lymphoma Society, National Cancer Institute, MD Anderson Cancer Center.
Qutrit Randomized Benchmarking Morvan, A.; Ramasesh, V. V.; Blok, M. S. ...
Physical review letters,
05/2021, Letnik:
126, Številka:
21
Journal Article
Recenzirano
Odprti dostop
Ternary quantum processors offer significant potential computational advantages over conventional qubit technologies, leveraging the encoding and processing of quantum information in qutrits ...(three-level systems). To evaluate and compare the performance of such emerging quantum hardware it is essential to have robust benchmarking methods suitable for a higher-dimensional Hilbert space. We demonstrate extensions of industry standard randomized benchmarking (RB) protocols, developed and used extensively for qubits, suitable for ternary quantum logic. Using a superconducting five-qutrit processor, we find an average single-qutrit process infidelity of 3.8×10−3. Through interleaved RB, we characterize a few relevant gates, and employ simultaneous RB to fully characterize crosstalk errors. Finally, we apply cycle benchmarking to a two-qutrit CSUM gate and obtain a two-qutrit process fidelity of 0.85. Our results present and demonstrate RB-based tools to characterize the performance of a qutrit processor, and a general approach to diagnose control errors in future qudit hardware.
Previous research has identified how menstruation is an important factor in both attempted and completed suicides for women. The purpose of this review was to outline (a) the risk profile for ...suicidality in women who were identified to experience Premenstrual Dysphoric Disorder (PMDD), a condition characterized by severe physical and psychological changes that occur during the luteal menstrual phase, and (b) the implications of these findings for clinical practice. A systematic literature review was conducted using five databases to identify any peer-reviewed articles published between 1989 and 2019. Ten papers eligible for inclusion were identified: three pertaining to
suicide cognitions
, five to
suicide attempts
and two to both
cognitions
and
attempts
. Findings showed that suicidal thoughts, ideation, plans and attempts were strongly associated with experiences of PMDD and that these findings were independent of psychiatric co-morbidities. However, women with PMDD did not present with more severe risk profiles for suicide attempts (in terms of frequency, impulsivity and lethality) or make more frequent attempts during the luteal menstrual phase compared with suicide attempters without PMDD. Women with PMDD should be considered a high risk group for suicidality; thus, identifying and treating symptoms are vital in reducing suicide attempts. Implications for clinical practice are outlined in the discussion.
Regional climate modeling addresses our need to understand and simulate climatic processes and phenomena unresolved in global models. This paper highlights examples of current approaches to and ...innovative uses of regional climate modeling that deepen understanding of the climate system. High-resolution models are generally more skillful in simulating extremes, such as heavy precipitation, strong winds, and severe storms. In addition, research has shown that finescale features such as mountains, coastlines, lakes, irrigation, land use, and urban heat islands can substantially influence a region’s climate and its response to changing forcings. Regional climate simulations explicitly simulating convection are now being performed, providing an opportunity to illuminate new physical behavior that previously was represented by parameterizations with large uncertainties. Regional and global models are both advancing toward higher resolution, as computational capacity increases. However, the resolution and ensemble size necessary to produce a sufficient statistical sample of these processes in global models has proven too costly for contemporary supercomputing systems. Regional climate models are thus indispensable tools that complement global models for understanding physical processes governing regional climate variability and change. The deeper understanding of regional climate processes also benefits stakeholders and policymakers who need physically robust, high-resolution climate information to guide societal responses to changing climate. Key scientific questions that will continue to require regional climate models, and opportunities are emerging for addressing those questions.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Preclinical changes that precede the onset of symptoms and eventual diagnosis of Alzheimer's disease (AD) are a target for potential preventive interventions. A large body of evidence suggests that ...inflammation is closely associated with AD pathogenesis and may be a promising target pathway for such interventions. However, little is known about the association between systemic inflammation and preclinical AD pathophysiology. We first examined whether the acute-phase protein, alpha-2 macroglobulin (A2M), a major component of the innate immune system, was associated with cerebrospinal fluid (CSF) markers of neuronal injury in preclinical AD and risk of incident AD in the predictors of cognitive decline among normal individuals (BIOCARD) cohort. We find that A2M concentration in blood is significantly associated with CSF concentrations of the neuronal injury markers, tau and phosphorylated tau, and that higher baseline serum A2M concentration is associated with an almost threefold greater risk of progression to clinical symptoms of AD in men. These findings were replicated in the Alzheimer's Disease Neuroimaging (ADNI) study. Then, utilizing a systems level approach combining large multi-tissue gene expression datasets with mass spectrometry-based proteomic analyses of brain tissue, we identified an A2M gene network that includes regulator of calcineurin (RCAN1), an inhibitor of calcineurin, a well-characterized tau phosphatase. A2M gene and protein expression in the brain were significantly associated with gene and protein expression levels of calcineurin. Collectively these novel findings suggest that A2M is associated with preclinical AD, reflects early neuronal injury in the disease course and may be responsive to tau phosphorylation in the brain through the RCAN1-calcineurin pathway.
The dynamics of quantum information in strongly interacting systems, known as quantum information scrambling, has recently become a common thread in our understanding of black holes, transport in ...exotic non-Fermi liquids, and many-body analogs of quantum chaos. To date, verified experimental implementations of scrambling have focused on systems composed of two-level qubits. Higher-dimensional quantum systems, however, may exhibit different scrambling modalities and are predicted to saturate conjectured speed limits on the rate of quantum information scrambling. We take the first steps toward accessing such phenomena, by realizing a quantum processor based on superconducting qutrits (three-level quantum systems). We demonstrate the implementation of universal two-qutrit scrambling operations and embed them in a five-qutrit quantum teleportation protocol. Measured teleportation fidelitiesFavg=0.568±0.001confirm the presence of scrambling even in the presence of experimental imperfections and decoherence. Our teleportation protocol, which connects to recent proposals for studying traversable wormholes in the laboratory, demonstrates how quantum technology that encodes information in higher-dimensional systems can exploit a larger and more connected state space to achieve the resource efficient encoding of complex quantum circuits.
Top-down approaches to measure total integrated emissions provide verification of bottom-up, temporally resolved, inventory-based estimations. Aircraft-based measurements of air pollutants from ...sources in the Canadian oil sands were made in support of the Joint Canada–Alberta Implementation Plan for Oil Sands Monitoring during a summer intensive field campaign between 13 August and 7 September 2013. The measurements contribute to knowledge needed in support of the Joint Canada–Alberta Implementation Plan for Oil Sands Monitoring. This paper describes the top-down emission rate retrieval algorithm (TERRA) to determine facility emissions of pollutants, using SO2 and CH4 as examples, based on the aircraft measurements. In this algorithm, the flight path around a facility at multiple heights is mapped to a two-dimensional vertical screen surrounding the facility. The total transport of SO2 and CH4 through this screen is calculated using aircraft wind measurements, and facility emissions are then calculated based on the divergence theorem with estimations of box-top losses, horizontal and vertical turbulent fluxes, surface deposition, and apparent losses due to air densification and chemical reaction. Example calculations for two separate flights are presented. During an upset condition of SO2 emissions on one day, these calculations are within 5 % of the industry-reported, bottom-up measurements. During a return to normal operating conditions, the SO2 emissions are within 11 % of industry-reported, bottom-up measurements. CH4 emissions calculated with the algorithm are relatively constant within the range of uncertainties. Uncertainty of the emission rates is estimated as less than 30 %, which is primarily due to the unknown SO2 and CH4 mixing ratios near the surface below the lowest flight level.
Objective This study aimed to prospectively examine the impact of chronic vs pregnancy-onset habitual snoring on gestational hypertension, preeclampsia, and gestational diabetes. Study Design ...Third-trimester pregnant women were recruited from a large, tertiary medical center from March 2007 through December 2010 and screened for the presence and duration of habitual snoring, as a known marker for sleep-disordered breathing. Clinical diagnoses of gestational hypertension, preeclampsia, and gestational diabetes were obtained. Results Of 1719 pregnant women, 34% reported snoring, with 25% reporting pregnancy-onset snoring. After adjusting for confounders, pregnancy-onset, but not chronic, snoring was independently associated with gestational hypertension (odds ratio, 2.36; 95% confidence interval, 1.48–3.77; P < .001) and preeclampsia (odds ratio, 1.59; 95% confidence interval, 1.06–2.37; P = .024) but not gestational diabetes. Conclusion New-onset snoring during pregnancy is a strong risk factor for gestational hypertension and preeclampsia. In view of the significant morbidity and health care costs associated with hypertensive diseases of pregnancy, simple screening of pregnant women may have clinical utility.
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