Fish oil (n-3 fatty acids) in drug resistant epilepsy: a randomised placebo-controlled crossover study.

Backgroundn-3 fatty acids inhibit neuronal excitability and reduce seizures in animal models. High-dose fish oil has been explored in two randomised trials in drug resistant epilepsy with negative results. We performed a phase II randomised controlled crossover trial of low-dose and high-dose fish oil in participants with drug resistant epilepsy to explore whether low-dose or high-dose fish oil reduces seizures or improves cardiovascular health.MethodsRandomised placebo-controlled trial of low-dose and high-dose fish oil versus placebo (corn oil, linoleic acid) in 24 participants with drug resistant epilepsy. A three-period crossover design was utilised lasting 42 weeks, with three 10-week treatment periods and two 6-week washout periods. All participants were randomised in double-blind fashion to receive placebo, high dose or low dose in different sequences. The primary outcome was per cent change in total seizure frequency.FindingsLow-dose fish oil (3 capsules/day, 1080 mg eicosapentaenoic acid+docosahexaenoic acid) was associated with a 33.6% reduction in seizure frequency compared with placebo. Low-dose fish oil was also associated with a mild but significant reduction in blood pressure. High-dose fish oil was no different than placebo in reducing seizures or improving cardiac risk factors.InterpretationIn this phase II randomised crossover trial, low-dose fish oil was effective in reducing seizures compared with placebo. The magnitude of improvement is similar to that of recent antiepileptic drug trials in drug resistant epilepsy (DRE). The results indicate that low-dose fish oil may reduce seizures and improve the health of people with epilepsy. These findings justify a large multicentre randomised trial of low-dose fish oil (n-3 fatty acids <1080 mg/day) in drug resistant epilepsy.Trial registration numberNCT00871377

Three-Dimensional Cell Culture Assays: Are They More Predictive of In Vivo Efficacy than 2D Monolayer Cell-Based Assays?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140110/1/adt.2015.29001.rtd.pd

An operative approach to address severe genu valgum deformity in the Ellis-van Creveld syndrome

BACKGROUND: The genu valgum deformity seen in the Ellis-van Creveld syndrome is one of the most severe angular deformities seen in any orthopaedic condition. It is likely a combination of a primary genetic-based dysplasia of the lateral portion of the tibial plateau combined with severe soft-tissue contractures that tether the tibia into valgus deformations. Progressive weight-bearing induces changes, accumulating with growth, acting on the initially distorted and valgus-angulated proximal tibia, worsening the deformity with skeletal maturation. The purpose of this study is to present a relatively large case series of a very rare condition that describes a surgical technique to correct the severe valgus deformity in the Ellis-van Creveld syndrome by combining extensive soft-tissue release with bony realignment. METHODS: 1. Complete proximal to distal surgical decompression of the peroneal nerve. 2. Radical release and mobilization of the severe quadriceps contracture and iliotibial band contracture. 3. Distal lateral hamstring lengthening/tenotomy and lateral collateral ligament release. 4. Proximal and distal realignment of the subluxed/dislocated patella, medial and lateral retinacular release, vastus medialis advancement, patellar chondroplasty, medial patellofemoral ligament plication, and distal patellar realignment by Roux-Goldthwait technique or patellar tendon transfer with tibial tubercle relocation. 5. Proximal tibial varus osteotomy with partial fibulectomy and anterior compartment release. 6. Occasionally, distal femoral osteotomy. RESULTS: In all cases, the combination of radical soft-tissue release, patellar realignment and bony osteotomy resulted in 10° or less of genu valgum at the time of surgical correction. Complications of surgery included three patients (five limbs) with knee stiffness that was successfully manipulated, one peroneal nerve palsy, one wound slough and hematoma requiring a skin graft, and one pseudoarthrosis requiring removal of hardware and repeat fixation. At last follow-up, radiographic correction of no more than 20° of genu valgum was maintained in all but four patients (four limbs). Two patients (three limbs) had or currently require revision surgery due to recurrence of the deformity. CONCLUSION: The operative approach presented in this study has resulted in correction of the severe genu valgum deformity in Ellis-van Creveld syndrome to 10° or less of genu valgum at the time of surgery. Although not an outcomes study, a correction of no more than 20° genu valgum has been maintained in many of the cases included in the study. Further clinical follow-up is still warranted. LEVEL OF EVIDENCE: IV

Tactical Themes for Rangeland Research

The problems threatening the conservation and management of rangeland, over one-half of the world’s terrestrial surfaces, are significant and growing. Current assessments of drivers and externalities shaping these problems have resulted in strategies intended to result in sustainable development of these lands and their resources. However, how can individual scientists and individual research programs support the needed strategies and goals? What can we realistically contribute and accomplish? We believe that technology can connect individual scientists and their science to the problems manifest in rangelands over the world, in a more rapid exchange than has occurred in the past. Recognition of local challenges, innovations, and scientific tests of the effectiveness of our technological solutions to these problems can keep pace with rapid change and help us adapt to that change. However, to do this, we have to invest in a process of connecting science to landscapes. Our tactics are to link, openly and collaboratively, the scientific method to discrete, specific, managed landscapes. We term these collective tactics, our fundamental research theme, “Landscape Portals”. All of the elements of this theme exist currently, to various degrees, but they lack cohesion and interactive, real-time connections. Future investment requires two basic, tactical scientific behaviors: a post-normal application of science in support of land management by hypothesis and a scientific method modified to accommodate a data intensive scientific inquiry directed towards adaptive management. These behaviors support our “Landscape Portals” theme: science conducted in a highly interactive, transparent, data enriched, locally relevant, globally connected, popularly translated, and ecologically robust manner

AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.

Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (

TURBOMOLE: Today and Tomorrow

TURBOMOLE is a highly optimized software suite for large-scale quantum-chemical and materials science simulations of molecules, clusters, extended systems, and periodic solids. TURBOMOLE uses Gaussian basis sets and has been designed with robust and fast quantum-chemical applications in mind, ranging from homogeneous and heterogeneous catalysis to inorganic and organic chemistry and various types of spectroscopy, light–matter interactions, and biochemistry. This Perspective briefly surveys TURBOMOLE’s functionality and highlights recent developments that have taken place between 2020 and 2023, comprising new electronic structure methods for molecules and solids, previously unavailable molecular properties, embedding, and molecular dynamics approaches. Select features under development are reviewed to illustrate the continuous growth of the program suite, including nuclear electronic orbital methods, Hartree–Fock-based adiabatic connection models, simplified time-dependent density functional theory, relativistic effects and magnetic properties, and multiscale modeling of optical properties

A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia

Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL)1–3, but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the octapeptide domain of PAX5 that was found to segregate with disease in two unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p loss harbored somatic PAX5 substitutions affecting Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated that it had significantly reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5 in a new syndrome of susceptibility to pre-B cell neoplasia

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages