Functional assessment for acute stroke trials: properties, analysis, and application

A measure of treatment effect is needed to assess the utility of any novel intervention in acute stroke. For a potentially disabling condition such as stroke, outcomes of interest should include some measure of functional recovery. There are many functional outcome assessments that can be used after stroke. In this narrative review, we discuss exemplars of assessments that describe impairment, activity, participation, and quality of life. We will consider the psychometric properties of assessment scales in the context of stroke trials, focusing on validity, reliability, responsiveness, and feasibility. We will consider approaches to the analysis of functional outcome measures, including novel statistical approaches. Finally, we will discuss how advances in audiovisual and information technology could further improve outcome assessment in trials

Use of magnesium as a drug in chronic kidney disease

From chronic kidney disease (CKD) Stage 4 onwards, phosphate binders are needed in many patients to prevent the development of hyperphosphataemia, which can result in disturbed bone and mineral metabolism, cardiovascular disease and secondary hyperparathyroidism. In this review, we re-examine the use of magnesium-containing phosphate binders for patients with CKD, particularly as their use circumvents problems such as calcium loading, aluminum toxicity and the high costs associated with other agents of this class. The use of magnesium hydroxide in the 1980s has been superseded by magnesium carbonate, as the hydroxide salt was associated with poor gastrointestinal tolerability, whereas studies with magnesium carbonate show much better gastrointestinal profiles. The use of combined magnesium- and calcium-based phosphate binder regimens allows a reduction in the calcium load, and magnesium and calcium regimen comparisons show that magnesium may be as effective a phosphate binder as calcium. A large well-designed trial has recently shown that a drug combining calcium acetate and magnesium carbonate was non-inferior in terms of lowering serum phosphate to sevelamer-HCl and had an equally good tolerability profile. Because of the high cost of sevelamer and lanthanum carbonate, the use of magnesium carbonate could be advantageous and drug acquisition cost savings would compensate for the cost of introducing routine magnesium monitoring, if this is thought to be necessary and not performed anyway. Moreover, given the potential cost savings, it may be time to re-investigate magnesium-containing phosphate binders for CKD patients with further well-designed clinical research using vascular end points

A rigid triple of conjugacy classes in G 2

We produce a rigid triple of classes in the algebraic group G 2 in characteristic 5, and use it to show that the finite groups G 2(5 n ) are not (2, 5, 5)-generate

Liveweight gain per head and per ha throughout the year of lambs grazing conventional pastures and those that switch from grass to clover

Intensive lamb finishing requires a consistent supply of high quality forage throughout the year to regularly finish lambs. Per head and per ha liveweight gain of weaned lambs was compared in 13 batches of lambs on replicated irrigated farmlets for 2.5 years from conventional mixed tetraploid perennial ryegrasswhite clover pastures (Conv) and pastures that were pure white clover for spring and summer and switched to overdrilled Italian ryegrass for the winter (Switch). Seasonal differences in stocking rate (lambs/ha), liveweight gain per head and per ha were significant (P<0.05). Average daily liveweight gain/ha was significantly higher (6.01 versus 5.66 kg/ha/day for Switch and Conv, respectively, but the total grazing days were slightly lower on the Switch farmlets resulting in similar annualised liveweight gain per ha (1 800 kg) and net carcass weight (800 kg/ha) on both pasture treatments. The farmlets apparently utilised 10 000 kg DM/ha/yr of the 16 000 kg DM accumulated.This work was funded by an internal Lincoln University Research Grant INT4052

Controllable Non-Markovianity for a Spin Qubit in Diamond

We present a flexible scheme to realize non-artificial non-Markovian dynamics of an electronic spin qubit, using a nitrogen-vacancy center in diamond where the inherent nitrogen spin serves as a regulator of the dynamics. By changing the population of the nitrogen spin, we show that we can smoothly tune the non-Markovianity of the electron spin's dynamic. Furthermore, we examine the decoherence dynamics induced by the spin bath to exclude other sources of non-Markovianity. The amount of collected measurement data is kept at a minimum by employing Bayesian data analysis. This allows for a precise quantification of the parameters involved in the description of the dynamics and a prediction of so far unobserved data points.Comment: 12 pages, 9 figure, including supplemental materia

Surface-topography-induced enhanced transmission and directivity of microwave radiation through a subwavelength circular metal aperture

Copyright © 2004 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in Applied Physics Letters 84 (2004) and may be found at http://link.aip.org/link/?APPLAB/84/2040/1Strongly enhanced transmission of microwave radiation (λ0~5 mm) is observed through a single subwavelength circular aperture of diameter d = 2.5 mm in a metallic plate. The phenomenon is caused by resonant excitation of electromagnetic surface waves supported by four concentric grooves surrounding the aperture on the illuminated side of the sample. It is also shown that similar surface patterning on the output face of the sample results in very strong angular confinement (directivity) of the transmitted beam. A finite element code is used to investigate the electromagnetic fields on both the illuminated and the exit side of the structure, the predictions from which show excellent agreement with the experimental results

A rigid triple of conjugacy classes in G(2)

We produce a rigid triple of classes in the algebraic group G(2) in characteristic 5, and use it to show that the finite groups G(2)(5(n)) are not (2, 5, 5)-generated

Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease.

ObjectiveTo understand the safety, putaminal coverage, and enzyme expression of adeno-associated viral vector serotype-2 encoding the complementary DNA for the enzyme, aromatic L-amino acid decarboxylase (VY-AADC01), delivered using novel intraoperative monitoring to optimize delivery.MethodsFifteen subjects (three cohorts of 5) with moderately advanced Parkinson's disease and medically refractory motor fluctuations received VY-AADC01 bilaterally coadministered with gadoteridol to the putamen using intraoperative magnetic resonance imaging (MRI) guidance to visualize the anatomic spread of the infusate and calculate coverage. Cohort 1 received 8.3 × 1011 vg/ml and ≤450 μl per putamen (total dose, ≤7.5 × 1011 vg); cohort 2 received the same concentration (8.3 × 1011 vg/ml) and ≤900 μl per putamen (total dose, ≤1.5 × 1012 vg); and cohort 3 received 2.6 × 1012 vg/ml and ≤900 μl per putamen (total dose, ≤4.7 × 1012 vg). (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography (PET) at baseline and 6 months postprocedure assessed enzyme activity; standard assessments measured clinical outcomes.ResultsMRI-guided administration of ascending VY-AADC01 doses resulted in putaminal coverage of 21% (cohort 1), 34% (cohort 2), and 42% (cohort 3). Cohorts 1, 2, and 3 showed corresponding increases in enzyme activity assessed by PET of 13%, 56%, and 79%, and reductions in antiparkinsonian medication of -15%, -33%, and -42%, respectively, at 6 months. At 12 months, there were dose-related improvements in clinical outcomes, including increases in patient-reported ON-time without troublesome dyskinesia (1.6, 3.3, and 1.5 hours, respectively) and quality of life.InterpretationNovel intraoperative monitoring of administration facilitated targeted delivery of VY-AADC01 in this phase 1 study, which was well tolerated. Increases in enzyme expression and clinical improvements were dose dependent. ClinicalTrials.gov Identifier: NCT01973543 Ann Neurol 2019;85:704-714

Molecular phylogeny of diplomonads and enteromonads based on SSU rRNA, alpha-tubulin and HSP90 genes: Implications for the evolutionary history of the double karyomastigont of diplomonads

<p>Abstract</p> <p>Background</p> <p>Fornicata is a relatively recently established group of protists that includes the diplokaryotic diplomonads (which have two similar nuclei per cell), and the monokaryotic enteromonads, retortamonads and <it>Carpediemonas</it>, with the more typical one nucleus per cell. The monophyly of the group was confirmed by molecular phylogenetic studies, but neither the internal phylogeny nor its position on the eukaryotic tree has been clearly resolved.</p> <p>Results</p> <p>Here we have introduced data for three genes (SSU rRNA, α-tubulin and HSP90) with a wide taxonomic sampling of Fornicata, including ten isolates of enteromonads, representing the genera <it>Trimitus </it>and <it>Enteromonas</it>, and a new undescribed enteromonad genus. The diplomonad sequences formed two main clades in individual gene and combined gene analyses, with <it>Giardia </it>(and <it>Octomitus</it>) on one side of the basal divergence and <it>Spironucleus</it>, <it>Hexamita </it>and <it>Trepomonas </it>on the other. Contrary to earlier evolutionary scenarios, none of the studied enteromonads appeared basal to diplokaryotic diplomonads. Instead, the enteromonad isolates were all robustly situated within the second of the two diplomonad clades. Furthermore, our analyses suggested that enteromonads do not constitute a monophyletic group, and enteromonad monophyly was statistically rejected in 'approximately unbiased' tests of the combined gene data.</p> <p>Conclusion</p> <p>We suggest that all higher taxa intended to unite multiple enteromonad genera be abandoned, that <it>Trimitus </it>and <it>Enteromonas </it>be considered as part of Hexamitinae, and that the term 'enteromonads' be used in a strictly utilitarian sense. Our result suggests either that the diplokaryotic condition characteristic of diplomonads arose several times independently, or that the monokaryotic cell of enteromonads originated several times independently by secondary reduction from the diplokaryotic state. Both scenarios are evolutionarily complex. More comparative data on the similarity of the genomes of the two nuclei of diplomonads will be necessary to resolve which evolutionary scenario is more probable.</p