To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and ...zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies.
A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003.
All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome.
The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary.
Rapid time to treatment with thrombolytic therapy is associated with lower mortality in patients with acute myocardial infarction (MI). However, data on time to primary angioplasty and its ...relationship to mortality are inconclusive.
To test the hypothesis that more rapid time to reperfusion results in lower mortality in the strategy of primary angioplasty.
Prospective observational study of data collected from the Second National Registry of Myocardial Infarction between June 1994 and March 1998.
A total of 661 community and tertiary care hospitals in the United States.
A cohort of 27,080 consecutive patients with acute MI associated with ST-segment elevation or left bundle-branch block who were treated with primary angioplasty.
In-hospital mortality, compared by time from acute MI symptom onset to first balloon inflation and by time from hospital arrival to first balloon inflation (door-to-balloon time).
Using a multivariate logistic regression model, the adjusted odds of in-hospital mortality did not increase significantly with increasing delay from MI symptom onset to first balloon inflation. However, for door-to-balloon time (median time 1 hour 56 minutes), the adjusted odds of mortality were significantly increased by 41% to 62% for patients with door-to-balloon times longer than 2 hours (for 121-150 minutes: odds ratio OR, 1.41; 95% confidence interval CI, 1.08-1.84; P=.01; for 151-180 minutes: OR, 1.62; 95% CI, 1.23-2.14; P<.001; and for >180 minutes: OR, 1.61; 95% CI, 1.25-2.08; P<.001).
The relationship in our study between increased mortality and delay in door-to-balloon time longer than 2 hours (present in nearly 50% of this cohort) suggests that physicians and health care systems should work to minimize door-to-balloon times and that door-to-balloon time should be considered when choosing a reperfusion strategy. Door-to-balloon time also appears to be a valid quality-of-care indicator. JAMA. 2000.
To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and ...zonisamide-reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies.
A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003.
There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking.
The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary.
Cancer is characterised by DNA hypermethylation and gene silencing of CpG island-associated promoters, including tumour-suppressor genes. The methyl-CpG-binding domain (MBD) family of proteins bind ...to methylated DNA and can aid in the mediation of gene silencing through interaction with histone deacetylases and histone methyltransferases. However, the mechanisms responsible for eliciting CpG island hypermethylation in cancer, and the potential role that MBD proteins play in modulation of the methylome remain unclear. Our previous work demonstrated that MBD2 preferentially binds to the hypermethylated GSTP1 promoter CpG island in prostate cancer cells. Here, we use functional genetic approaches to investigate if MBD2 plays an active role in reshaping the DNA methylation landscape at this locus and genome-wide. First, we show that loss of MBD2 results in inhibition of both maintenance and spread of de novo methylation of a transfected construct containing the GSTP1 promoter CpG island in prostate cancer cells and Mbd2-/- mouse fibroblasts. De novo methylation was rescued by transient expression of Mbd2 in Mbd2-/- cells. Second, we show that MBD2 depletion triggers significant hypomethylation genome-wide in prostate cancer cells with concomitant loss of MBD2 binding at promoter and enhancer regulatory regions. Finally, CpG islands and shores that become hypomethylated after MBD2 depletion in LNCaP cancer cells show significant hypermethylation in clinical prostate cancer samples, highlighting a potential active role of MBD2 in promoting cancer-specific hypermethylation. Importantly, co-immunoprecipiation of MBD2 shows that MBD2 associates with DNA methyltransferase enzymes 1 and 3A. Together our results demonstrate that MBD2 has a critical role in 'rewriting' the cancer methylome at specific regulatory regions.
We analyze the trajectories of 313 particles seen in the near‐Bennu environment between December 2018 and September 2019. Of these, 65% follow suborbital trajectories, 20% undergo more than one ...orbital revolution around the asteroid, and 15% directly escape on hyperbolic trajectories. The median lifetime of these particles is ∼6 hr. The trajectories are sensitive to Bennu's gravitational field, which allows us to reliably estimate the spherical harmonic coefficients through degree 8 and to resolve nonuniform mass distribution through degree 3. The particles are perturbed by solar radiation pressure, enabling effective area‐to‐mass ratios to be estimated. By assuming that particles are oblate ellipsoids of revolution, and incorporating photometric measurements, we find a median axis ratio of 0.27 and diameters for equivalent‐volume spheres ranging from 0.22–6.1 cm, with median 0.74 cm. Our size distribution agrees well with that predicted for fragmentation due to diurnal thermal cycling. Detailed models of known accelerations do not produce a match to the observed trajectories, so we also estimate empirical accelerations. These accelerations appear to be related to mismodeling of radiation pressure, but we cannot rule out contributions from mass loss. Most ejections take place at local solar times in the afternoon and evening (12:00–24:00), although they occur at any time of day. We independently identify ten ejection events, some of which have previously been reported. We document a case where a particle ricocheted off the surface, revealing a coefficient of restitution 0.57±0.01 and demonstrating that some apparent ejections are not related to surface processes.
Plain Language Summary
The Origins, Spectral Interpretation, Resource Identification, Security, Regolith Explorer (OSIRIS‐REx) mission discovered that near‐Earth asteroid (101955) Bennu is periodically ejecting small particles from its surface, placing it in the uncommon class of “active asteroids.” We linked together individual detections of ejected particles and used numerical models of the forces acting on them to ascertain their trajectories and fates. We found that most particles have suborbital trajectories, meaning they fall back to Bennu's surface shortly after being ejected, but some orbit Bennu for days at a time, and some escape directly into space. From the particle trajectories, we are able to estimate their sizes (comparable to pebbles, from a few millimeters to a few centimeters in diameter) and shapes (probably flake like). Their trajectories also make it possible to estimate Bennu's gravity field more precisely than spacecraft measurements and help shed light on the possible causes of the ejections.
Key Points
Most of the 313 particles we study have suborbital trajectories, but some orbit Bennu and others directly escape
The particles appear to have flake‐like shapes and have effective diameters 0.22–6.1 cm with median 0.74 cm
Ejections tend to take place in the local afternoon and evening but can occur anytime
•Nitrogen (N) and irrigation management are critical in the production of durum wheat.•A 2-year study in Arizona USA assessed N fertilizer and irrigation in durum wheat.•Recovery efficiency of added ...N was high in this system at greater than 70%.•Grain N was maximum at a lower water level (50% of full irrigation).•Optimal grain yields and grain protein are achievable.
Nitrogen and irrigation management are crucial in the production of high protein irrigated durum wheat (Triticum durum Desf.) in arid regions. However, as the availability of irrigation water decreases and potential costs and regulation of nitrogen (N) increase, there is a need to better understand how irrigation levels interacts with N fertilizer rates. A two-year field experiment was conducted in Maricopa, Arizona USA on a Casa Grande sandy loam to assess effects of N fertilizer and irrigation rates on grain yield, grain N, canopy temperatures yellow berry, and N use efficiency. Five rates of N fertilizer as urea ammonium nitrate (0, 84, 168, 252, and 336kgNha−1) were applied in three equal splits at Zadoks stages 30, 32, and 39. Ten un-randomized, sequential rates of irrigation ranging from 0.35 to 1.14 fraction of a non-deficit base irrigation treatment (maintained >45% soil water depletion) were applied by sequentially varying the nozzles in a gradient in an overhead sprinkler system. Irrigation plus rain ranged from 230 to 660mm in the first season, and 180 to 600mm in the second season. Grain yield was maximum in 2013 at the 252kgNha−1 fertilizer rate and at the 10th water level (1.14 irrigation), and between 168kg and 252kgNha−1at the 8th water level (1.0 irrigation) in 2014. The maximum grain yield of 7500kgha−1 in 2013 was reduced to 5000kgha−1 in 2014 due to a warmer, shorter growing season. Economic optimum N rate was at water level 8 both years (196 and 138kgNha−1 in 2013, and 2014, respectively). Recovery efficiency of added N was high in this system (i.e., >70%) at N fertilizer and water levels that maximized biomass and grain yields. Grain N was maximum at a lower water level (level 3 or 0.50–0.54 irrigation), was positively affected by N fertilizer rate, and was negatively related to yellow berry incidence. Canopy temperature minus air temperature values decreased linearly with increasing irrigation level. Nitrogen fertilizer applications reduced canopy temperature when water levels >0.54 and 0.69 irrigation fraction in 2013, and 2014, respectively. The study results suggested that canopy temperature and weather data that reflects the grain-filling period could be used to improve irrigation and N management, respectively. In short, irrigated durum wheat growers on this soil would achieve the economically optimum grain yield, with the least risk of yield or protein reduction, by applying 200kgNha−1 at the base irrigation level which maintains root zone soil moisture depletion below 45%.
The purification of nucleic acids from microbial and mammalian cells is a crucial step in many biological and medical applications. We have developed microfluidic chips for automated nucleic acid ...purification from small numbers of bacterial or mammalian cells. All processes, such as cell isolation, cell lysis, DNA or mRNA purification, and recovery, were carried out on a single microfluidic chip in nanoliter volumes without any pre- or postsample treatment. Measurable amounts of mRNA were extracted in an automated fashion from as little as a single mammalian cell and recovered from the chip. These microfluidic chips are capable of processing different samples in parallel, thereby illustrating how highly parallel microfluidic architectures can be constructed to perform integrated batch-processing functionalities for biological and medical applications.
Influenza A viruses (IAV) and SARS-CoV-2 can spread via liquid droplets and aerosols. Face masks and other personal protective equipment (PPE) can act as barriers that prevent the spread of these ...viruses. However, IAV and SARS-CoV-2 are stable for hours on various materials, which makes frequent and correct disposal of these PPE important. Metal ions embedded into PPE may inactivate respiratory viruses, but confounding factors such as adsorption of viruses make measuring and optimizing the inactivation characteristics difficult. Here, we used polyamide 6.6 (PA66) fibers containing embedded zinc ions and systematically investigated if these fibers can adsorb and inactivate SARS-CoV-2 and IAV H1N1 when woven into a fabric. We found that our PA66-based fabric decreased the IAV H1N1 and SARS-CoV-2 titer by approximately 100-fold. Moreover, we found that the zinc content and the virus inactivating property of the fabric remained stable over 50 standardized washes. Overall, these results provide insights into the development of reusable PPE that offer protection against RNA virus spread.
Abstract
Atmospheric electric field measurements from the Concordia station on the Antarctic Plateau are compared with those from Vostok (560 km away) for the period of overlap (2009–11) and to ...Carnegie (1915–29) and extended Vostok (2006–11) measurements. The Antarctic data are sorted according to several sets of criteria for rejecting local variability to examine a local summer-noon influence on the measurements and to improve estimates of the global signal. The contribution of the solar wind influence is evaluated and removed from the Vostok and Concordia measurements. Simultaneous measurements yield days when the covariability of the electric field measurements at Concordia and Vostok exceeds 90%, as well as intervals when significant local variability is apparent. Days of simultaneous changes in shape and mean level of the diurnal variation, as illustrated in a 5-day sequence, can be interpreted as due to changes in the relative upward current output of the electrified cloud generators predominating at low latitudes. Smaller average local meteorological influences are removed from the larger Vostok dataset, revealing changes in the shape of monthly average diurnal variations, which are similarly attributed to changes in predominantly low-latitude convection from month to month.
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