Towards dynamical network biomarkers in neuromodulation of episodic migraine

Computational methods have complemented experimental and clinical neursciences and led to improvements in our understanding of the nervous systems in health and disease. In parallel, neuromodulation in form of electric and magnetic stimulation is gaining increasing acceptance in chronic and intractable diseases. In this paper, we firstly explore the relevant state of the art in fusion of both developments towards translational computational neuroscience. Then, we propose a strategy to employ the new theoretical concept of dynamical network biomarkers (DNB) in episodic manifestations of chronic disorders. In particular, as a first example, we introduce the use of computational models in migraine and illustrate on the basis of this example the potential of DNB as early-warning signals for neuromodulation in episodic migraine.Comment: 13 pages, 5 figure

Membranes for CO2 capture - report on pilot plant tests

Although the main part of the world has now accepted the fact that the global climate change is due to human activities, we will not be able to switch gear and only go for “green energy” without fossil fuels for still many decades. One way of contributing to combat the climate change is hence to capture the CO2 from fossil fuel flue gases, and either find ways to utilize the CO2 or sequestrate it in aquifers or depleted oil fields, while we slowly develop a “green way of living”. Membranes will for sure represent one of the emerging technologies to be used for CO2 capture. Today there are a few pilot installations around the world using different types of membranes, to demonstrate and learn the best way of optimize such a capture plant – in Norway there are two of such kind; one at a cement factory in Brevik in South Norway and one at a test center at Tiller in Trondheim. At the cement plant the CO2 concentration in the flue gas can be close to 20 vol%, while at the Tiller plant there is a possibility to vary the CO2 concentration over a range of 8 – 12vol%. At the cement plant the flue gas contains quite a few unwanted components, while at Tiller the flue gas is relatively “clean”. The type of membrane installed at these two sites is hollow fiber modules where the support fiber is polysulfone (PSf) and the coated mebrane is a polyvinylamine (PVAm). The technique for applying the coating is not straight forward, and an efficient flue gas separation depends strongly on a successful coating procedure. Going from lab tests using a few cm2 up to several m2 of a commercial scale module is extremely challenging. The tests are being performed with 2 or 3 modules in parallel or series, but not yet as a complete two-stage process. Based on obtained results, a full scale process will be simulated. Preliminary results using only one stage at Tiller are already documenting an encouraging 58% CO2 in permeate from 7% CO2 in feed line. The PVAm membrane is based on facilitated transport of the CO2 through the membrane, which means that water needs to be handled in the separation process – this has again a large influence on the engineering design of the process and process operation parameters. The presentation will highlight and report some results and challenges from these two tests sites. Acknowledgement The GASSNOVA projects 229949 and 249036 are highly recognized for contributions from the CLIMIT-Demo program in the Norwegian Research Council, Air Products and Chemicals, Inc. (USA), Air Products AS (Norway), Alberta Funders (Canada), Statoil ASA, NORCEM (Heidelberg Cement), SINTEF Materials and Chemistry, DNV GL (The Netherlands)

Effect of water interactions on Polyvinylamine at different pH for Membrane gas separation

Polyvinylamine (PVAm) is a linear polyelectrolyte type of polymer which is water-soluble with highest contents of primary amine. It has been attractive in different fields such as: biomedical applications [1], encapsulation [2], oil recovery [3], and primarily it has extensively been used as a fixed-site–carrier polyvinylamine membrane for carbon dioxide separation and capture. A thin selective layer on polysulfone support for CO2 Separation membranes[4, 5] has been successfully used in composite flat sheet and hollow fiber membranes. The amine group plays the role as the carrier of the gas, increasing the transport performance of the membrane by chemical and physical forces. PVAm composite membrane in dry condition will separate according to solution-diffusion mechanism only. It was however documented by Kim et al. in 2004 [4] that by allowing the membrane to be exposed gas with high relative humidity, the separation performance increased exponentially[4-6]. Through these efforts, it is needed to develop a greater understanding of the relationships between the structure and the interfacial properties of PVAm – water surface. The degree of hydrophilicity manipulation of a given surface necessarily requires understanding the micro-scale principles that, in turn, control the macro-scale surface wetting behavior. See Fig. 1. Please click Additional Files below to see the full abstract

Genome analysis of Phytophthora cactorum strains associated with crown- and leather-rot in strawberry

Phytophthora cactorum has two distinct pathotypes that cause crown rot and leather rot in strawberry (Fragaria × ananassa). Strains of the crown rot pathotype can infect both the rhizome (crown) and fruit tissues, while strains of the leather rot pathotype can only infect the fruits of strawberry. The genome of a highly virulent crown rot strain, a low virulent crown rot strain, and three leather rot strains were sequenced using PacBio high fidelity (HiFi) long read sequencing. The reads were de novo assembled to 66.4–67.6 megabases genomes in 178–204 contigs, with N50 values ranging from 892 to 1,036 kilobases. The total number of predicted complete genes in the five P. cactorum genomes ranged from 17,286 to 17,398. Orthology analysis identified a core secretome of 8,238 genes. Comparative genomic analysis revealed differences in the composition of potential virulence effectors, such as putative RxLR and Crinklers, between the crown rot and the leather rot pathotypes. Insertions, deletions, and amino acid substitutions were detected in genes encoding putative elicitors such as beta elicitin and cellulose-binding domain proteins from the leather rot strains compared to the highly virulent crown rot strain, suggesting a potential mechanism for the crown rot strain to escape host recognition during compatible interaction with strawberry. The results presented here highlight several effectors that may facilitate the tissue-specific colonization of P. cactorum in strawberry.publishedVersio

Sphenopalatine ganglion stimulation for cluster headache, results from a large, open-label European registry

Abstract Background Cluster headache (CH) is a disabling primary headache disorder characterized by severe periorbital pain. A subset of patients does not respond to established pharmacological therapy. This study examines outcomes of a cohort of mainly chronic CH patients treated with sphenopalatine ganglion (SPG) stimulation. Methods Patients were followed in an open-label prospective study for 12 months. Ninety-seven CH patients (88 chronic, 9 episodic) underwent trans-oral insertion of a microstimulator targeting the SPG. Patients recorded stimulation effect prospectively for individual attacks. Frequency, use of preventive and acute medications, headache impact (HIT-6) and quality of life measures (SF-36v2) were monitored at clinic visits. Per protocol, frequency responders experienced ≥ 50% reduction in attack frequency and acute responders treated ≥ 50% of attacks. HIT-6 responders experienced an improvement ≥ 2.3 units and SF-36 responders ≥ 4 units vs. baseline. Results Eighty-five patients (78 chronic, 7 episodic) remained implanted and were evaluated for effectiveness at 12 months. In total, 68% of all patients were responders, 55% of chronic patients were frequency responders and 32% of all patients were acute responders. 67% of patients using acute treatments were able to reduce the use of these by 52% and 74% of chronic patients were able to stop, reduce or remain off all preventive medications. 59% of all patients were HIT-6 responders, 67% were SF-36 responders. Conclusions This open-label registry corroborates that SPG stimulation is an effective therapy for CH patients providing therapeutic benefits and improvements in use of medication as well as headache impact and quality of life

Pervasive fungicide resistance in Botrytis from strawberry in Norway: Identification of the grey mould pathogen and mutations

Control of grey mould, caused by Botrytis spp., is a major challenge in open field strawberry production. Botrytis was isolated from plant parts collected from 19 perennial strawberry fields with suspected fungicide resistance in the Agder region of Norway in 2016. Resistance to boscalid, pyraclostrobin and fenhexamid was high and found in 89.1%, 86.0% and 65.4% of conidia samples, respectively. Multiple fungicide resistance was common; 69.6% of conidia samples exhibited resistance to three or more fungicides. Botrytis group S and B. cinerea sensu stricto isolates were obtained from 19 and 16 fields, respectively. The sdhB, cytb, erg27 and mrr1 genes of a selection of isolates were examined for the presence of mutations known to confer fungicide resistance to boscalid, pyraclostrobin, fenhexamid and pyrimethanil plus fludioxonil, respectively. Allele-specific PCR assays were developed for efficient detection of resistance-conferring mutations in cytb. Among B. cinerea isolates, 84.7%, 86.3% and 61.3% had resistance-conferring mutations in sdhB, cytb and erg27, respectively. A triplet deletion in mrr1, resulting in ΔL497, commonly associated with the multidrug resistance phenotype MDR1h, was detected in 29.2% of Botrytis group S isolates. High frequencies of resistance to several fungicides were also detected in Botrytis from both imported and domestically produced strawberry transplants. Fungicide resistance frequencies were not different among fields grouped by level of grey mould problem assessed by growers, indicating factors other than fungicide resistance contributed to control failure, a fact that has important implications for future management of grey mould.publishedVersio

Effectiveness of transcranial direct current stimulation alone or preceding cognitive-behavioral management for chronic low back pain: a sham-controlled, double blinded randomized controlled trial

Objective To evaluate the effectiveness of transcranial direct current stimulation alone and in combination with cognitive behavioural management in patients with non-specific chronic low back pain. Design Double blind parallel group randomised controlled trial with six months’ follow-up conducted May 2011-March 2013. Participants, physiotherapists, assessors, and analyses were blinded to group allocation. Setting Interdisciplinary chronic pain centre. Participants 135 participants with non-specific chronic low back pain >12 weeks were recruited from 225 patients assessed for eligibility. Intervention Participants were randomised to receive anodal (20 minutes to motor cortex at 2 mA) or sham transcranial direct current stimulation (identical electrode position, stimulator switched off after 30 seconds) for five consecutive days immediately before cognitive behavioural management (four week multidisciplinary programme of 80 hours). Main outcomes measures Two primary outcome measures of pain intensity (0-100 visual analogue scale) and disability (Oswestry disability index) were evaluated at two primary endpoints after stimulation and after cognitive behavioural management. Results Analyses of covariance with baseline values (pain or disability) as covariates showed that transcranial direct current stimulation was ineffective for the reduction of pain (difference between groups on visual analogue scale 1 mm (99% confidence interval −8.69 mm to 6.3 mm; P=0.68)) and disability (difference between groups 1 point (−1.73 to 1.98; P=0.86)) and did not influence the outcome of cognitive behavioural management (difference between group 3 mm (−10.32 mm to 6.73 mm); P=0.58; difference between groups on Oswestry disability index 0 point (−2.45 to 2.62); P=0.92). The stimulation was well tolerated with minimal transitory side effects. Conclusions This results of this trial on the effectiveness of transcranial direct current stimulation for the reduction of pain and disability do not support its clinical use for managing non-specific chronic low back pain. Trial registration Current controlled trials ISRCTN89874874

Evaluation of Ethiopian maize cultivars for resistance to Fusarium verticillioides and fumonisin accumulation

The objective of this study was to find sources of resistance to Fusarium ear rot and fumonisin accumulation in maize germplasm. Totally 15 maize cultivars were evaluated by means of silk channel inoculation using a fumonisin producing F. verticillioides isolate in field trials during 2013 and 2014 cropping seasons. Fusarium ear rot severity was determined at harvest, and fumonisin content was quantified using competitive Enzyme Linked Immunosorbent Assay (ELISA). The percentage of infected kernels per maize ear after inoculation, ranged from 5% to 60% in 2013 and from 3% to 40% in 2014. Fumonisin accumulation in maize cultivars ranged from 2700 to 76300 µg/kg in 2013 and from 1800 to 52700 µg/kg in 2014. Maize cultivars Berihu, Melkassa-2, Melkassa-7, Melkassa-4, BHQP542 and MHQ-138 showed low level of ear rot (3.9% to 22.9%) and total fumonisins (2300 to 17300 µg/kg) across the two years experiment. Cultivars that had low disease severity are useful in breeding programs aiming at developing cultivars resistance to fumonisin accumulation

Detection of total fumonisins produced by Fusarium verticillioides (Sacc) isolates from maize kernels in Ethiopia

Fusarium verticillioides is the most common fungal pathogen of maize in Ethiopia. Many strains of this pathogen produce fumonisin myotoxins that are harmful to human and animal health. This study was conducted to determine the fumonisin-producing ability of isolates of F. verticillioides isolated from maize kernels collected from different maize- growing areas of the country. Eighty F. verticillioides isolates were grown on autoclaved maize cultures for one month, and the fumonisin content was quantified using Enzyme Linked Immunosorbent Assay (ELISA). All the 80 isolates evaluated were able to produce detectable levels of total fumonisins in the maize culture with values ranging from 0.25 to 38.01 mg of the toxin per kg of culture material (fungal biomass and maize kernels). The mean levels of total fumonisins produced by the F. verticillioides isolates were not significantly (p>0.05) different among maize growing areas, however, the total fumonisins levels produced by isolates obtained from the same area as well as agroecological zones were wide-ranging. The results indicate that the majority (57.5%) of the F. verticillioides isolates associated with maize grains in Ethiopia produced total fumonisins >4 mg/kg, while 35% of the isolates produced total fumonisins <2 mg/kg. The widespread occurrence of higher fumonisin-producing strains across all maize-growing areas in Ethiopia indicates a possible food safety risk. Thus, efforts should be made to prevent the spread of this fungus with good agronomic practices and to implore all possible ways to avoid maize contamination with fumonisin both in the field and in storage.publishedVersio

Pathogenicity, host specificity and genetic diversity in Norwegian isolates of Microdochium nivale and Microdochium majus

Microdochium majus and Microdochium nivale cause serious disease problems in grasses and cereal crops in the temperate regions. Both fungi can infect the plants during winter (causing pink snow mould) as well as under cool humid conditions during spring and fall. We conducted a pathogenicity test of 15 M. nivale isolates and two M. majus isolates from Norway at low temperature on four different grass cultivars of Lolium perenne and Festulolium hybrids. Significant differences between M. nivale isolates in the ability to cause pink snow mould were detected. The M. nivale strains originally isolated from grasses were more pathogenic than isolates from cereals. The genetic diversity of M. nivale and M. majus isolates was studied by sequencing four genetic regions; Elongation factor-1 alpha (EF-1α), β-tubulin, RNA polymerase II (RPB2) and the Internal Transcribed Spacer (ITS). Phylogenetic trees based on the sequences of these four genetic regions resolved M. nivale and M. majus isolates into separate clades. Higher genetic diversity was found among M. nivale isolates than among M. majus isolates. M. nivale isolates revealed genetic differences related to different host plants (grasses vs. cereals) and different geographic regions (Norway and UK vs. North America). Sequence results from the RPB2 and β-tubulin genes were more informative than those from ITS and EF-1α. The genetic and phenotypic differences detected between Norwegian M. nivale isolates from cereals and grasses support the assumption that host specialization exist within M. nivale isolates.publishedVersio